Download Annual Report 2015

German Center
for Infection Research
ANNUAL REPORT 2015
Title image: Effective against Tuberculosis: cyclohexylgriselimycin, a variant of griselimycin (shown here as a blue, white and
red ball-and-stick model) binds to so-called DNA clamp of tuberculosis bacteria at two sites (shown here in the grey protein
structure and in cartoon images on the left). Griselimycins block the “DNA clamp” in a way that prevents binding of bacterial
DNA polymerase, and consequently inhibit bacterial genome replication.
DZIF at a glance
The German Center for Infection Research (DZIF) coordinates and oversees the
strategic planning of translational infection research in Germany.
Its mission is to translate results from basic infection research into clinical
research and bring them to the patient.
35 DZIF research centres work concertedly against the global threat presented by
infectious diseases.
DZIF ANNUAL REPORT 2015
Table of contents
Editorial ...................................................................................................................................................................................................................... 3
About the DZIF ................................................................................................................................................................................................. 4
Science – Translation in focus
Emerging Infections ............................................................................................................................................................................ 6
Tuberculosis ................................................................................................................................................................................................... 8
Malaria ............................................................................................................................................................................................................. 10
HIV ........................................................................................................................................................................................................................ 12
Hepatitis ......................................................................................................................................................................................................... 14
Gastrointestinal Infections ..................................................................................................................................................... 16
Infections of the immunocompromised Host ................................................................................................... 18
Healthcare-associated and Antibiotic-resistant bacterial Infections .................................. 20
Novel Antiinfectives ........................................................................................................................................................................ 22
Research infrastructures
Product Development Unit .................................................................................................................................................... 24
Clinical Trial Unit .................................................................................................................................................................................. 25
African Partner Institutions ................................................................................................................................................... 26
Natural Compound Library .................................................................................................................................................... 27
Biobanking .................................................................................................................................................................................................. 28
Bioinformatics ........................................................................................................................................................................................ 29
DZIF Academy .............................................................................................................................................................................................. 30
Collaborations at the DZIF ............................................................................................................................................................ 31
DZIF Highlights 2015 ........................................................................................................................................................................... 32
Science and public .................................................................................................................................................................................... 34
External collaborations ..................................................................................................................................................................... 36
German Health Research Centres ...................................................................................................................................... 39
Facts and figures
Organisation and bodies ............................................................................................................................................................ 40
Partner sites and member establishments .......................................................................................................... 43
Finances ......................................................................................................................................................................................................... 46
Personnel and awards ................................................................................................................................................................... 48
Indicators 2015 .................................................................................................................................................................................... 50
Publications ................................................................................................................................................................................................ 52
Member establishments ............................................................................................................................................................ 55
Imprint ..................................................................................................................................................................................................................... 56
Dirk Heinz, Ulrike Protzer, Martin Krönke
Last year, a major topic on the G7 Summit’s agenda was
the global threat of infectious diseases. The participating
nations committed themselves to reinforcing their
research activities; to developing new antibiotics,
vaccines, alternative treatment and diagnostic methods
in international collaborations. This is in 100 percent
alignment with the DZIF’s mission—it has aimed to achieve
these goals with an internationally oriented, translational
approach from the start.
The DZIF successfully dedicated itself to helping in the
Ebola epidemic in West Africa. Based on clinical trials
conducted by DZIF staff in Hamburg und Lambaréné,
the company Merck applied for approval at the American
Food and Drug Authority (FDA) for the rVSV-Zebov
vaccine which is to be used against Ebola in future.
However, outbreaks of other infectious diseases like the
current Zika epidemic show that there is no time to rest
on one’s laurels. Researchers and health politicians are
increasingly being challenged by the increase of zoonoses
transmitted from animals to humans. In 2015, the FriedrichLoeffler-Institut, Federal Research Institute for Animal
Health joined the DZIF, adding a new member to the “One
Health” concept. The Robert Koch Institute has also been
on board since 2015. It sets the stage for ideal connections
to aspects of public health and epidemiological topics.
The rise of multidrug-resistance, against which even lastresort antibiotics are becoming ineffective, was in the
public focus once again in 2015. Especially reports about
transferable colistin resistance in gram-negative bacteria
in China were cause for great concern, not only amongst
specialists. DZIF researchers also confirmed the existence
of the responsible resistance gene mrc-1 in Germany.
Knowledge about this gene’s transmission routes could
help curb its spread.
The Federal Institute for Drugs and Medical Devices
(BfArM) has now become the third new member of the
DZIF’s Product Development Unit, complementing the
unit as a regulatory authority and significantly increasing
the prospects of success for product development
projects. Consequently, DZIF researchers have succeeded
in advancing the development of tuberculosis agents and
broad spectrum antibiotics to the stage of being accepted
in pharmaceutical company funding programmes and
by other external partners (the European Innovative
Medicines Initiative (IMI), amongst others). A strategic
partnership with a vaccine manufacturing company has
been initiated for the upcoming clinical trials on a MERS
coronavirus vaccine—another impressive example that
the DZIF is an attractive industrial partner.
Finally, international review committee audits conducted
in 2015 acknowledged the DZIF’s outstanding success.
At the same time, this audit encouraged developing
the approach further and setting new ambitious goals.
Consequently, epidemiological and preventive strategies
will be given higher importance at the DZIF in future;
vaccines and developing antibiotics will gain a broader
platform.
This Annual Report will give you an impression of the
advances in infection research. We hope you enjoy
reading it.
DZIF e.V. Executive Board
Prof Martin Krönke
Prof Ulrike Protzer
Prof Dirk Heinz
EDITORIAL
Editorial
3
ABOUT DZIF
DZIF ANNUAL REPORT 2015
Successful exchange at the joint 2015 DZIF and DGI Annual Meeting in Munich 2015.
4
About the DZIF
Research without borders:
united against infections
Viruses, bacteria and parasites know no boundaries: they are transregionally mobile and
threaten global health. From AIDS to malaria to tuberculosis—infectious diseases remain
one of the major causes of death worldwide. Although vaccines, antibiotics and improved
hygiene have made many infectious diseases less threatening, the pathogens continue to
develop new survival strategies. Scientists at the German Center for Infection Research
(DZIF) tackle this challenge and develop new drugs, vaccines and preventive measures
against infectious diseases.
A united scientific community is the best approach to
tackling major infectious disease challenges. For this
reason, the German Federal Ministry of Education and
Research (BMBF) established the DZIF as part of an
organised research alliance and one of six German Centers for Health Research (DZG) in 2011. This alliance is
growing—since 2015, the Friedrich-Loeffler-Institut
(FLI), the Robert Koch Institute (RKI) and the German
Federal Institute for Drugs and Medical Devices (BfArM)
have joined. With this, the DZIF now unites over 600
members of staff across 35 establishments and seven
partner sites.
Translational orientation
The mutual goal: to rapidly translate basic research findings
into clinical applications. The DZIF Main Office, located
in Braunschweig, provides researchers with support for
initiating and conducting projects. This contributes to
improved diagnostic, prevention and treatment methods
getting from bench to bedside more smoothly and rapidly.
The Press Office reports important research findings
to relevant professional and public media. The DZIF’s
activities are 90% funded by the federal government and
10% from national funds.
Services for everyone
Prerequisites for providing quality-assured answers to
research questions are accessibility to collections relevant
to infectious diseases as well as scientific and administrative expertise. To this effect, the DZIF has established special infrastructures which are available to all the scientists:
the “Natural Compound Library” with extensive natural
substance collections, biobanks with different patient and
pathogen samples, as well as a bioinformatics platform.
Beyond this, clinical trial units support the researchers in
testing trial subjects, and the Product Development Unit
provides advice for all stages of drug development, starting
with ideas for a drug or vaccine through to approval stages.
The African Partner Institutions provide the opportunity to
research diseases which occur rarely in our geographical
region in areas where they occur frequently.
Furthering collaborations
Networking with different partners and external scientific establishments or industrial companies further
expands the scope of the DZIF’s expertise. The DZIF’s
involvement in national, European and international networks also increases its visibility in the scientific sector,
enabling collaborations for future research projects.
Growing this network contributes to decreasing the risk
associated with infectious disease pathogens, and to mitigating and combating disease.
DZIF groups its research activities into nine
research fields and eight research infrastructures,
internally called Thematic Translational Units (TTUs)
and Translational Infrastructures (TIs):
Research fields
• Emerging infections
• Tuberculosis
• Malaria
• HIV
• Hepatitis
• Gastrointestinal Infections
• Infections of the immunocompromised Host
• Healthcare-associated and Antibiotic-resistant bacterial Infections
• Novel Antiinfectives
Research Infrastructures
• Product Development Unit
• Clinical Trial Unit
• African Partner Institutions
• Natural Compound Library
• Biobanking
• Bioinformatics
• Epidemiology (since 2016)
• Pathogen Repository (since 2016)
• DZIF Academy
Promoting the next generation
Our integrative approach is also attractive for upcoming
generations of scientists. PhD stipends and special
workshops, as well as other funding possibilities at the
DZIF Academy enable doctors to better combine clinical
work and research. Laboratory rotations permit young
scientists to gain insight into other research fields and
methods. Funding programmes for young mothers
support combining family with a scientific career.
ABOUT DZIF
United across various establishments
Universities, hospitals, research institutes and specialised federal research institutions—the DZIF unites very
different establishments across its seven partner sites
in Germany: Bonn-Cologne, Gießen-Marburg-Langen,
Hamburg-Lübeck-Borstel (recently including the island
of Riems), Hannover-Braunschweig, Heidelberg, Munich
and Tübingen. The topic of research determines who
works together. Scientists across the partner sites dedicate themselves to a pathogen or a specific question in
the field of infection research.
5
SCIENCE – TRANSLATION IN FOCUS
DZIF ANNUAL REPORT 2015
Helpers on the ground: The mobile field laboratory “EmLab” was in Guinea at the start of the Ebola epidemic.
6
Emerging Infections
Prepared for all
(emergency) events
Emerging infections are often caused by viruses like Ebola, MERS and Zika.
They can be transmitted from animals to humans, causing unknown diseases that spread
quickly and require rapid action. At the research field “Emerging Infections”, DZIF
researchers take on this difficult task, with staff from research, hospital and the public
health service sector working together closely.
In the research field “Emerging Infections” scientists
contribute their expertise in diagnostics, epidemiology and prophylaxis of different infectious diseases. The
aim of this research field is to reduce the time between
the emergence of a new epidemic and the use of effective drugs to counteract it. To this effect, the scientists
develop a basis for broad-spectrum antiviral drugs and
vaccine platforms.
Preparing for emergencies
Dr Michael Mühlebach and his research team from the
Paul-Ehrlich-Institut (PEI) are working on such a “vaccine
platform”. They insert selected genetic sequences of an
emerging virus into the commonly known measles vaccine.
“Platform vaccines are advantageous, because the basic
vaccine features are already known and the new virus
parts can be incorporated comparatively quickly,” explains
SCIENCE – TRANSLATION IN FOCUS
clinical efficacy testing of the vaccine candidate “favipiravir”
against Ebola in patients in Guinea. In retrospect, Günther
is certain that, “The DZIF made an important contribution
to the fight against the 2014/2015 Ebola epidemic, which
will also advance research.”
In the DZIF-initiated EBOKON project, DZIF members
participated in a global WHO study on clinical phase I
testing of the Ebola vaccine candidate “rVSV-ZEBOV”,
amongst other things. A vaccine approval by the American
authority FDA is hoped for early 2017.
MERS coronaviruses (blue) on epithelial camel cells.
Goals for 2016 at a glance
Mühlebach. He describes how this works using the MERS
coronavirus (MERS-CoV), which causes the Middle East
respiratory syndrome, as an example. The syndrome, first
described in humans in 2012, can cause severe respiratory
tract infections that are, in part, fatal. After identifying
MERS-CoV as the cause of the disease, a collaboration of
several DZIF research teams succeeded in developing a
vaccine against MERS-CoV based on a measles vaccine.
For this, they inserted the gene coding for the MERSCoV envelope protein into the measles vaccine virus. In
mouse tests, the novel vaccine triggered a strong immune
response and resulted in high protection. Mühlebach
believes, “The measles viruses we used could also serve as a
vaccine platform for protection against other new viruses.
“This project’s rapid success is especially thanks to many
collaborations with colleagues and their complementary
expertise.”
Good networking for unexpected emergencies
Prof Stephan Günther is of a similar opinion: “The
networking within the DZIF played a central role in the
fight against the 2014/2015 Ebola epidemic.” He is Head
of the Department of Virology at the Bernhard Nocht
Institute for Tropical Medicine (BNITM) in Hamburg, and
led several projects during the Ebola outbreak. Together
with DZIF colleagues from Marburg, Munich and Bonn, his
research team was one of the first to set up mobile field
laboratories in Guinea. In the European project EMLab,
they conducted on-site testing for Ebola on about 20,000
patient samples. In a follow-up EU project, they traced the
virus’ genetic changes and its spread in the region by means
of genome sequence analysis of the collected samples and
with mathematical models. Prof Günther and a team of
DZIF scientists developed a mouse model in order to more
precisely understand the course of disease, and supported
•Preparation of a clinical phase I trial
(first-in-man) of an MVA-based vaccine
candidate against the MERS coronavirus.
•Preclinical evaluation of a substance with broad spectrum effects against enteroviruses, alpha and beta coronaviruses.
•Establishing a tick, livestock and domestic animal sample collection for detecting
viruses.
Coordinator:
Prof Dr Stephan Becker
Marburg
7
SCIENCE – TRANSLATION IN FOCUS
DZIF ANNUAL REPORT 2015
Physicians (Christoph Lange in the image) focus on tailored treatment regimens.
8
Tuberculosis
Individual concepts for
a complex disease
With over nine million cases and more than 1.5 million deaths per year, tuberculosis (TB)
is one of the most dangerous infections worldwide. It most frequently affects the lungs,
and additionally also organs like lymph nodes, bones and the nervous system. Experts
face major challenges with the spread of multi-drug resistant (MDR) and extensively
resistant (XDR) tuberculosis bacteria. At the research field “Tuberculosis”, DZIF scientists
use molecular biology verification methods, develop new active agents and individually
tailored treatment regimens to tackle these problems.
At the partner sites Hamburg-Lübeck-Borstel, BonnCologne, Hannover-Braunschweig, Munich and Tübingen,
DZIF researchers have dedicated themselves to fighting
tuberculosis, with a particular focus on difficult-to-treat
cases of M/XDR-TB. The number of known cases in Europe
has increased markedly over the last years: from about
28,000 in 2009 to 40,000 registrations in 2014. MDR/
XDR-TB strains are spreading rapidly, especially in Eastern
Europe and Asia. In contrast to the commonly known TB
bacteria, MDR/XDR-TB strains have undergone genetic
changes making them resistant to the common antibiotics.
With the rise of this resistance, side effects, costs and
treatment duration are also increasing. Especially the
most hard-hit regions lack resources to effectively treat
patients with M/XDR tuberculosis and to curb its spread.
Currently, less than half the patients are curable.
Interdisciplinary consultation—individual treatment
“The chances of cure can be significantly increased,” says
Prof Christoph Lange, Head of Clinical Infectious Diseases
at the Research Center Borstel, one of the leading
international establishments in this field. The DZIF’s
Clinical Center for Tuberculosis (ClinTB) was established
there in order to provide optimal treatment for patients
with M/XDR-TB. Physicians can obtain round-the-clock
telephone advice from the information hotline. In 2015
alone, a team of six physicians responded to over 1,000
clinical queries. Since 2015, the centre has been working
together with a team of infectious disease specialists,
pulmonologists, surgeons, microbiologists and public
health sector staff to tackle special M/XDR tuberculosis
cases. In an online platform, colleagues can submit a
patient’s medical history, laboratory values and x-rays and
obtain expert recommendations within 72 hours. “We are
increasingly using tailored treatment concepts in which
the antibiotics are individually selected” explains Lange.
The centre is also developing guidelines for dealing with
M/XDR-TB. Additionally, it is involved with internal DZIF
training, and organises symposiums for physicians from
practices, hospitals and scientific establishments. “With
the ClinTB treatment concept, basic research is being
translated into personalised medicine,” explains Lange,
“through which we are currently creating the best chances
of cure in the world for the affected patients.”
Initiative for innovative active agents
DZIF scientists like Prof Michael Hölscher, Head of the
Department of Infectious Diseases and Tropical Medicine
at the LMU Munich, are directly involved with the
development of new drugs. In this lengthy and complex
process they collaborate with the Euro-African network
PanACEA and the Hans Knöll Institute in Jena. Together
SCIENCE – TRANSLATION IN FOCUS
Medical students in Namibia explaining an x-ray to a patient.
with DZIF scientists, a benzothiazinone which had been
discovered there was developed further into a candidate
drug called BTZ043. It inhibits an enzyme specifically
required by tuberculosis bacteria for cell wall synthesis. “In
preclinical studies on animal models, BTZ043 effectivity
was comparable to the standard drugs and was non-toxic
and well tolerated,” reports Hölscher. “The special thing is
that the candidate drug is also effective against the tested
M/XDR-TB strains. The clinical phase I trial is scheduled
for mid-2017 and it involves several DZIF establishments,”
explains Hölscher. “With the DZIF’s infrastructure, we
have the possibility of advancing a product’s development
up to clinical phase III.”
Besides this, DZIF researchers investigate new diagnostic
tests for simple detection of resistance genes, and search
for biomarkers to monitor treatment. Furthermore, they
conduct epidemiological analyses of the spread of M/
XDR-TB strains and are establishing an international
clinical trial centre (InternatTBTrial).
Goals for 2016 at a glance:
•Precisely determine the specific hereditary information of a patient’s tuberculosis pathogens in order to enable individual adjustment of treatment.
• Identify biomarkers which can provide precise information about a therapy’s success.
• Complete the preclinical phase of a potential tuberculosis drug.
Coordinator:
Prof Dr Stefan Niemann
Borstel
9
SCIENCE – TRANSLATION IN FOCUS
DZIF ANNUAL REPORT 2015
Staff at the Institute for Tropical Medicine in Tübingen preparing the medication for a new malaria drug trial.
10
Malaria
Fighting malaria with
new drugs
Malaria remains one of the major global infectious diseases. Although, according to
the WHO, there was a remarkable decline between 2000 and 2015, with a 37 percent
reduction in the number of new cases and a 60 percent reduction in mortality, the
World Health Organisation still estimated 214 million new cases of infection and
438,000 deaths for 2015. The malaria parasites, which are transmitted by mosquitoes,
especially affect young children in Africa. In the research field “Malaria”, DZIF
scientists develop new preventive and therapeutic agents, and test measures to
prevent the spread of this tropical disease.
DZIF scientists in Hamburg, Heidelberg and Tübingen
face several challenges: the available diagnostics in many
of the affected regions often cannot differentiate between
malaria and other febrile illnesses, which impedes targeted
treatment. Despite many years of research, there is still
no vaccine with sufficient protection available. Mosquitos
are becoming less and less sensitive to insecticides,
and regional genetic differences in the pathogen and in
populations additionally complicate treatment. Further
obstacles include co-infections with other pathogens and
resistance to the conventional malaria drugs. Currently,
there are several active agent candidates in development.
Preventing malaria with new drugs
Dr Benjamin Mordmüller and his team from the Institute
for Tropical Medicine, Tübingen University, are testing
a new agent that can both prevent and treat malaria. It
blocks an enzyme that is important for the pathogen’s
reproduction. The substance, DSM265, specifically acts
against these parasite enzymes. First studies on safety
and dose determination for malaria treatment have had
positive results, based on which Mordmüller and his team
are testing its prophylactic efficacy in a clinical doubleblind study for the first time. Healthy volunteers who had
previously not been exposed to malaria are administered
DSM265 and then infected with malaria parasites under
controlled conditions. In groups, six volunteers each take
the agent and two others a placebo. From the first day, the
researchers examine blood samples from the subjects on
a daily basis. As soon as pathogens are identified in the
blood, the affected volunteer is additionally administered
a rapid-acting malaria drug. “However, this has only been
necessary once up to now,” reports Mordmüller, who
is optimistic in general. “The substance has shown no
side effects and is well-tolerated.” Additionally, the first
evaluations have indicated good efficacy. Dr Mordmüller
envisions this substance being able to protect babies and
pregnant women against malaria.
Predicting with mathematical models
Scientists from the Bernhard Nocht Institute for Tropical
Medicine in Hamburg (BNITM) support their colleagues
in Tübingen with mathematical bioinformatics methods.
The aim of their work is to describe courses of infection
as well as the spread and human immune responses to
infection more precisely. Their studies provide data that
helps differentiate between malaria and other febrile
infectious diseases. “Epidemiologists are included in the
study planning and conduction from the start, so that
they can help determine appropriate data collection
methods,” emphasizes Ralf Krumkamp, infectious
SCIENCE – TRANSLATION IN FOCUS
Ralf Krumkamp and his colleagues are responsible for data
analysis and mathematical modelling.
disease epidemiologist at the BNITM. In doing so, they
determine potential sources of error in advance, monitor
data collection and help evaluate complex data sets.
“Identifying potential sources of error and taking these
into consideration when analysing the data is important,”
the scientist explains. A further method is mathematical
modelling: “The method is similar to those used for
weather forecasts,” compares Ralf Krumkamp, “but here
we try and depict infections’ transmission dynamics and
the effects of control measures.”
Beyond this, the DZIF scientists are testing an alternative
vaccination method with weakened malaria parasites.
After testing preventive and therapeutic agents on
volunteers who have not been exposed to malaria, they
will continue testing the method on local volunteers
at the African Partner Institutions. Alongside this, the
researchers are investigating the regional spread of
malaria subtypes, their drug resistance and immunity
in the population in epidemiological studies. These data
are important for planning and implementing targeted
measures against the pathogens.
Goals for 2016 at a glance
• A promising vaccination approach, which has already been successfully tested for safety and efficacy in Tübingen, is to undergo further trials so that it can be tested as a vaccination schedule in phase III.
• The preclinical phase of a potential drug against severe malaria is to be largely completed.
• Diagnostic biomarkers that enable a differentiation between malaria and sepsis in ill children and adolescents in Africa are to be selected from well-defined clinical samples.
Coordinator:
Prof Dr Peter Kremsner
Tübingen
11
SCIENCE – TRANSLATION IN FOCUS
DZIF ANNUAL REPORT 2015
Artistic warning: AIDS information campaign in Mbeya, Tanzania.
12
HIV
Cure is the declared
goal
In 2015, over 36 million people worldwide were infected with the human immunodeficiency
virus (HIV). 1.1 million died of the consequence of this infection—the acquired immune
deficiency syndrome AIDS. The disease can be treated with antiviral therapy which
increases life expectancy and decreases the rate of new infections. However, to date, neither
a cure nor a vaccine against the virus exist. Different subtypes and the virus’s variability
make accomplishing these goals difficult. DZIF scientists in the research field “HIV” are
pursuing gene therapy approaches to cure the disease, they also aim to strengthen prevention
and enable a long, complication-free life.
Large regional differences in the spread of HIV demand a
nuanced approach to HIV infection: in industrial nations
like Germany, prevention and long-term treatment are in
the foreground. In developing countries, AIDS has taken
on the dimension of a widespread common disease—
accompanied by a dramatically decreased life expectancy,
societal problems and economic consequences. Here, the
situation demands affordable medication and improved
medical infrastructures that permit effective treatment.
Successful HIV treatment decreases the viral load in
every individual and with that also the risk of infecting
other people, including mother-to-child transmission.
Earlier treatment of babies with HIV
According to the UN, 150,000 children contracted HIV
in 2015—most of them in Africa. Often, these children
become infected in the womb, during birth or through
breastfeeding. Without timely HIV testing and initiation
of treatment, more than half of the infected babies die
before their second birthday. DZIF scientists at the LMU
Munich and African partner institutions in Tanzania test
the requirements for early treatment. “We know from
studies in adults: the earlier HIV treatment is initiated,
the higher are the chances of cure or remission, i.e. a
reduction of the viral load and viral reservoir,” explains
Dr Arne Kroidl, head of the study, “and a prerequisite for
this is detecting the virus as early as possible.” While HIV
testing in Africa is usually only conducted four weeks after
birth, the DZIF team examined 600 mother-child pairs
from birth. Mobile equipment for molecular diagnostics
was used for reliable confirmation of HIV infection in the
babies. This mini laboratory can also be used by trained
people in rural regions. “In this way, infected babies could
be identified and treated earlier,” says Kroidl.
Furthermore, DZIF researchers have developed an
enzyme which very specifically excises HIV proviruses
from infected cells’ genetic material, constituting a new
approach to curing HIV. Further projects of the research
field “HIV” include patient cohorts for investigating innate
immunity and protective antiviral factors against HIV.
Goals for 2016 at a glance
•Establish a cohort of newly HIV infected patients for future clinical trials on eliminating latent HIV infection, in collaboration with practices specialised in HIV treatment.
•Improved diagnostics for immediate detection of HIV in newborns in Africa so as to enable earlier treatment initiation.
•Excise and destroy HIV genomes in latently infected cells using optimised designer nucleases and new vectors for gene therapy.
Coordinator:
Prof Dr Hans-Georg Kräusslich
Using HIV neutralising antibodies for prevention
and treatment
Prof Florian Klein, Head of the Laboratory of Experimental
Immunology at the University of Cologne is specialised in
human immune responses to HIV, particularly antibody
responses: “His scientific work on broadly neutralising
antibodies has great implications for vaccine development
and innovative curative HIV treatment,” concluded the
German AIDS Society jury and awarded Klein the 2015
science award. Klein uses findings from his research at the
Rockefeller University in New York, where he investigated
HIV infection in humanised mice. “These mice possess
human immune cells and can therefore be infected with
HIV. This permits us to investigate the disease very well,
Heidelberg
SCIENCE – TRANSLATION IN FOCUS
Early detection of HIV: a little blood taken from a newborn’s heel
provides further information.
particularly new treatment approaches,” explains Klein. In
2015, he returned on a Heisenberg professorship to the
University of Cologne, where he had previously studied
and worked as a physician for several years. Here, Klein
supervises an immunology laboratory, numerous clinical
trials and a DZIF funded central humanised mouse unit.
As of the end of 2016, this new DZIF establishment will
enable scientists to investigate infections in vivo in order
to gain new insights for the prevention and treatment of
HIV and other infectious diseases.
13
SCIENCE – TRANSLATION IN FOCUS
DZIF ANNUAL REPORT 2015
Diagnosing hepatitis infections as early as possible is an important goal.
14
Hepatitis
Many approaches to a
treacherous disease
Infections with hepatitis virus types A to E cause liver inflammation (hepatitis). Worldwide,
400 million people are infected, and 95 percent are unaware of their infection. Initially,
viral hepatitis usually exhibits no symptoms, yet it causes over 1.4 million deaths per year—
about as many as caused by HIV and tuberculosis. In the research field “Hepatitis”, DZIF
scientists improve diagnostics, research new drugs and conduct epidemiological studies in
order to prevent and cure this liver disease.
People who are infected with hepatitis B (HBV), C (HCV)
and/or D (HDV) are particularly at risk. These virus types can
develop chronic courses of disease and cause liver cirrhosis
and liver cancer if left untreated. There is a preventive
vaccine against HBV which also protects against a coinfection with HDV. Antiviral drugs can supress HBV but do
not cure the disease. The treatment of HCV has improved
enormously thanks to new active agents: over 90 percent
of patients can be completely cured—the treatment costs,
however, are still very high. More prevention as well as more
affordable drugs for difficult-to-treat cases in economically
disadvantaged countries are urgently needed.
One active agent—many applications
Scientists from TWINCORE and the Hannover Medical
School (MHH) analysed substance collections in order
to find alternative, economic therapies for patients
with chronic HCV infection. Their idea: to avoid drug
development costs and rapidly find new, more economic
anti-HCV agents by testing active substances that have
already been approved for other diseases. They tested 23
drugs and found “flunarizine”, a drug for migraine, to be
effective against HCV as it inhibits the fusion of the virus
with its target cell. “Flunarizine stops the viral entry of
HCV genotype II,” explains Paula Perin. Working from the
TWINCORE Division of Experimental Virology she won
the 2015 MHH PhD Award for this discovery. Although
the agent is only effective against one of seven HCV
genoptypes, the project has been a success considering
that about 16 million patients could be treated with it.
“And beyond that, together with collaborative partners,
we can try and change the active agent to also make it
effective against other HCV genotypes,” explains Prof
Thomas Pietschmann, Head of the Division.
Therapy for transplant patients
The researchers also found an improved treatment for
particularly difficult-to-treat hepatitis patients at the
MHH Department of Gastroenterology, Hepatology
and Endocrinology. This group includes chronic HCV
patients with a severe course of disease, subsequent
liver transplant and re-infection of the new liver. The
physicians were faced with a problem on their quest for
improved treatment: on the one hand, transplant patients
have to take immunosuppressants to weaken their
immune systems and avoid rejection of the transplanted
liver. On the other hand, immunosuppressants often
“Myrcludex B”, which was developed at the DZIF, is a
promising candidate drug for treating hepatitis B and D.
This virus blocker inhibits hepatitis B and D virus entry
into the liver cell, and is now undergoing clinical trials at
the University of Heidelberg.
Goals for 2016 at a glance
•Develop new strategies for curing hepatitis B in collaboration with the French ANRS.
•Determine how often hepatitis C strains resistant to the new antiviral drugs occur in Germany.
•Develop new high-throughput methods to find specific agents against the hepatitis D virus.
Coordinator:
Prof Dr Michael Manns
Hannover
SCIENCE – TRANSLATION IN FOCUS
Liver cells infected with hepatitis C virus: the cell nuclei are shown
in blue, viral protein is red. Cellular lipid droplets that are essential
for HCV replication are shown in green. Flunarizine inhibits virus
entry into the cells.
impede antiviral treatment. In a retrospective analysis,
Dr Sandra Ciesek and Dr Thomas von Hahn, head of the
research group at the MHH Department, compared the
clinical data of treated patients. They found that patients
who had received the immunosuppressant “rapamycin”
had an improved course of disease. Additional molecular
biological testing revealed the drug’s concomitant effect:
“rapamycin” inhibits mTOR, an enzyme that is important
for both the immune system and HCV replication. “mTOR
inhibitors kill two birds with one stone, because they
simultaneously inhibit both the immune defence system
and the virus,” explains von Hahn.
15
SCIENCE – TRANSLATION IN FOCUS
DZIF ANNUAL REPORT 2015
A vaccine is being developed against the gastric pathogen Helicobacter pylori (in the image) and is now going into clinical trials.
16
Gastrointestinal Infections
Promising alternatives
to antibiotics
Gastrointestinal infections are caused by numerous bacteria, viruses, and parasites.
According to the WHO, around 1.5 million people worldwide die of the consequences of
diarrhoeal disease each year. Children in developing countries under the age of five are
particularly affected by diarrhoea, vomiting, malnutrition and death. Additionally, at least
one million people die of the consequences of Helicobacter pylori infection each year.
DZIF scientists in the research field “Gastrointestinal Infections” improve prophylaxis,
diagnostics and treatment of bacterial infections of the gastrointestinal tract.
Diarrhoeal disease is caused by pathogens like
Salmonella, Escherichia coli and rotaviruses. The course
of disease depends on the virulence (harmfulness) of
the pathogens on the one hand, and on the infected
person’s immune system and treatment on the other. To
date, hardly any effective vaccines exist. Antibiotics that
are effective against many pathogens are available, but
they often cause equal damage to both the pathogenic
and useful organisms, facilitating the spread of antibiotic
resistance and difficult-to-treat pathogens. This is why
DZIF scientists intensively research alternative treatment options.
Alternative paths to finding drugs
DZIF researchers from the partner sites Tübingen,
Hannover-Braunschweig and Munich are pursuing
a promising strategy with so-called pathoblockers.
These do not kill the bacteria but specifically block their
pathogenic features. The researchers have identified
several target sites that could be used for blocking. “One
could, for example, inhibit the adhesins which bacteria
use to attach themselves to their host cells,” explains
Dr Monika Schütz from the University of Tübingen.
The microbiologist and her team are now looking for
suitable agents that are effective against adhesins and
other target sites. They have already systematically
searched through 20,000 natural substances and “small
molecules” in the DZIF’s extensive active substance
libraries—and are now getting more support. Out of
several other applications, their screening system was
selected for an innovative drug research programme by
a European Lead Factory expert panel. An international
consortium consisting of 30 partners from industry
and science now advises them on searching for
agent candidates and drug development. Schütz is
enthusiastic, “This is a major step. It provides us a
professional environment in which we can test around
500,000 substances for their efficacy.”
Alternative vaccines for therapy
Helicobacter pylori is also an important gastrointestinal
tract pathogen. The bacteria cause infections in half of
the human population. They are considered the main
cause of gastric ulcers and gastric cancer, and account
for 900,000 cases of disease worldwide each year.
There are antibiotics available to treat this infection and
its consequences, but they are becoming increasingly
ineffective due to growing resistance. DZIF scientists,
led by Prof Markus Gerhard from TU Munich, are
therefore developing a vaccine treatment: “We want to
vaccinate adults with H. pylori infections who have not
In the field of diagnostics, DZIF researchers look for
biomarkers that provide information about individual
sensitivities to specific gut bacteria. These serve as a
basis for developing new treatment options to protect
the gut flora and/or strengthen the body’s immune
system. A further approach is in the field of microbiome
research. Here, DZIF scientists are investigating the
composition of the natural stomach and gut flora and
the role this plays in gastrointestinal diseases.
SCIENCE – TRANSLATION IN FOCUS
The quest for new active substances requires screening many
potential substances.
previously had gastric ulcers or gastric cancer,” explains
Gerhard. These gastric bacteria produce an enzyme
called gamma-glutamyl transpeptidase, or gGT in short,
which inhibits the human cellular immune response.
If the body is administered modified gGT as a vaccine,
it develops antibodies that inactivate this bacterial
enzyme, hence reactivating the patient’s immune
response to protect the body against H. pylori. “The
vaccine is now being prepared in a spin-off company
after which first clinical trials will be initiated and we
could have a suitable vaccine in six to eight years,”
believes Gerhard.
Goals for 2016 at a glance
•Patient recruitment for the SPECTRUM trial is to be completed. The trial aims to identify components of the gut microbiome that influence infections with Clostridium difficile.
•Clinical phase I trials with the vaccine candidate against Helicobacter pylori will be initiated.
•The screening phase for the majority of pathoblocker target sites is to be completed.
Coordinator:
Prof Dr Sebastian Suerbaum
Hannover
17
SCIENCE – TRANSLATION IN FOCUS
DZIF ANNUAL REPORT 2015
Cell cultures in an incubator (in the photo: Dr Chiara Rancan).
18
Infections of the immunocompromised Host
Protecting vulnerable people –
supporting immune systems
The survival chances of many patients have improved thanks to medical advances in
cancer therapy, transplantation and intensive care medicine. However, these therapies
often weaken the immune system, making patients more susceptible to infectious
diseases. In the research field “Infections of the immunocompromised Host”, DZIF
scientists develop new methods to protect vulnerable patients from infection and to
support their immune systems.
Elderly people and patients with chronic diseases like
cancer or diabetes have weakened immune systems. The
number of immunocompromised patients in hospitals will
increase due to demographic developments. For these
patients, pathogens which are normally harmless can
become life threatening and almost uncontrollable with
conventional antibiotics. DZIF researchers analyse the
changes in the immune systems of immunocompromised
patients as these constitute one of the main reasons for
disease development.
Uncovering immune defence mechanisms
To this effect, the research group “Immune Control of
Viral Infections”, led by Dr Andreas Moosmann at the
Helmholtz Zentrum München, was established at the
DZIF in 2015. “Latent viral infections constitute a major
challenge,” explains Moosmann. These include EpsteinBarr virus (EBV) infections which are often symptom
free as healthy peoples’ immune systems are able to keep
the virus under control. However, the virus remains in
the cells and if the immune system is then weakened by
therapies, the virus may start replicating uncontrollably
and contribute to the development of cancer. Moosmann
and his team elucidated this mechanism with regard to
T lymphocytes. These “T cells” are able to identify viral
antigens on the surface of infected cells and destroy them,
or at least inhibit viral replication. EBV effectively protects
itself against this mechanism with a “magic cloak” making
it invisible to the destructive T cells. Moosmann and his
colleague Dr Chiara Rancan found out that the viral protein
LMP2A is responsible for this. “With this, we also hope to
find new approaches to treatment,” says Moosmann.
Supporting the immune system with adoptive
cellular therapy
Prof Dirk Busch, Director of the Institute of Medical
Microbiology, Immunology and Hygiene at the TU Munich
is also pursuing novel treatment approaches. Busch and his
team discovered so-called “central T memory cells (TCMs)”
which have the features of tissue stem cells. If patients with
weakened immune systems receive pathogen-specific
TCMs from a donor, they can regain complete immunity
to specific infectious disease pathogens, such as the
cytomegalovirus (CMV) or EBV. The patient’s immune
system is specifically enhanced by the donor cells, similar
to what happens with a passive vaccination. Together
with colleagues from the USA and industrial partners
(Juno Therapeutics), the researchers developed methods
for preparing donor TCMs for clinical application. Busch
is certain, “We believe that it is particularly important to
select the correct original cells for manufacturing optimal
cell products for therapy.” They are now being tested
in first clinical trials in the DZIF project “Prophylactic
The research field “Infections of the immunocompromised
Host” is also establishing a national transplant cohort. To
this effect, DZIF scientists are collecting clinical data and
biological samples from transplant patients throughout
Germany. They use these to examine which factors
influence infection susceptibility and organ function.
Furthermore, the researchers also investigate diagnostic
biomarkers which can be used to assess risks of infection,
and develop new antiinfectives against particularly
common viral diseases in immunocompromised patients.
Goals for 2016 at a glance
•Identify new biomarkers which can be used to assess the risk of infection with a specific pathogen in immunocompromised patients.
•Significantly increase the number of patient and biological samples in the DZIF transplant cohort collection, after completion of the pilot phase.
•Identify new inhibitors for clinically relevant viral infections in immunosuppressed patients.
•GMP manufacture of the components for a new EBV vaccine.
•Initiation of an adoptive T cell therapy trial for the prophylactic treatment of infections in allogeneic stem cell transplants (PACT Trial).
Coordinator:
Prof Dr Dirk Busch
München
SCIENCE – TRANSLATION IN FOCUS
The viral protein LMP2A (violet) changes the surface composition
of the infected cell. This impairs infection recognition by immune
cells (T cells).
Adoptive Transfer of Central memory T cells (PACT)”.
Busch is confident: “Basically, a single T cell could suffice for
transferring effective and permanent immune protection
against specific pathogens and tumour antigens.”
19
SCIENCE – TRANSLATION IN FOCUS
DZIF ANNUAL REPORT 2015
Very special juice: blood culture bottles in an incubator.
20
Healthcare-associated and Antibiotic-resistant bacterial Infections
Against the spread of
antibiotic resistance
In Germany, approximately half a million people contract bacterial infections in hospitals
every year. Treating them not only requires a lot of time, but also generates costs
ranging in the millions. According to estimates by the German National Reference Center
for Surveillance of Nosocomial Infections, up to 15,000 patients die of hospital-acquired
infections per year. Pathogens that are resistant to antibiotics play a major role in this.
In the research field “Healthcare-associated and Antibiotic-resistant bacterial Infections”,
DZIF scientists investigate how antibiotic resistance develops and what strategies could
prevent it.
Hospital-acquired, so-called nosocomial, infections often
occur in intensive care wards in patients who have just
had surgery or who are vulnerable. As these patients
are at risk, they are often administered antibiotics early
on. However, the pathogens are increasingly becoming
resistant: the conventional drugs are becoming ineffective. Inappropriate use of antibiotics in human
and veterinary medicine additionally facilitates the
development of resistance, and a lack of hygiene and
global mobility accelerate their spread. Many resistant
pathogens, such as methicillin-resistant Staphylococcus
aureus bacteria (MRSA) and so-called ESBL-producing
Enterobacteriaceae which produce broad-spectrum
beta lactamase are often only sensitive to last-resort
antibiotics.
Resistance gene against last-resort
antibiotic discovered
However, bacteria even challenge last-resort antibiotics.
Dr Can Imirzalioglu from the University of Gießen and his
team of DZIF scientists made an astonishing discovery:
they discovered that the “mcr-1 gene”, which makes
bacteria resistant to colistin, also exists in Germany. A
human sample from 2014 contained bacteria carrying an
mcr-1 gene which was not only resistant to colistin but also
to almost all other last-resort antibiotics. “It is alarming
that these resistance genes are also transferable between
different bacteria and therefore spread easily,” says
Imirzalioglu. The microbiologist deems responsible the
so-called plasmids, small ring shaped DNA molecules in
the bacteria which are easily transferrable. A prerequisite
for rapidly identifying this mcr-1 gene was searching
through a large database containing gene sequences
of multidrug-resistant bacteria from both humans and
animals. In Germany, colistin is used more frequently in
veterinary medicine. The mcr-1 gene had already been
identified in isolates in 2010. Dr Imirzalioglu believes that
a transmission from animals to humans is possible and
concludes: “We should reduce the use of colistin in animal
feed.”
The DZIF research field also actively focuses on prevention
and is developing guidelines for antibiotic stewardship
programmes taking place outside hospitals. The findings
in a current study underline the importance of controlling
antibiotic prescription in practices.
Goals for 2016 at a glance
• Develop and test new substances for completely eradicating staphylococci.
• Investigate the effectiveness of contact isolation on the spread of vancomycin-resistant enterococci (VRE).
• Establish a surveillance system for the monthly use of antibiotics in participating centres.
Coordinator:
Decreasing antibiotic use reduces evolution
of resistance
Are patients outside hospitals carriers of multidrugresistant pathogens as well, and/or do they themselves
import them into hospitals? Dr Axel Hamprecht and Prof
Harald Seifert from the University Hospital Cologne and
their team of DZIF scientists investigated this question
in the antibiotic therapy optimisation study (ATHOS).
Six German university hospitals participated in the study
led by the Cologne microbiologists. On admission to
hospital, over 4,000 adults were tested for multidrug-
Prof Dr Evelina Tacconelli
Tübingen
SCIENCE – TRANSLATION IN FOCUS
Multidrug-resistant Enterobacteriaceae in a petri dish.
resistant gut bacteria by means of stool samples and
rectal swabs. The researchers placed a particular focus
on so-called third-generation cephalosporin-resistant
Enterobacteriaceae (3GCREB) and vancomycin-resistant
enterococci (VRE). In order to find causal factors for the
development of such pathogens, the patients additionally
completed a supplementary questionnaire on hospital
stays and lifestyle habits. “Patients who have taken
antibiotics and travellers outside of Europe are at higher
risk,” says Hamprecht, highlighting two of the findings.
“It is surprising that almost ten percent of the study
participants were already 3GCREB carriers on admission.
With so many people affected, the strategy of isolating
patients in hospitals is no longer viable; additionally,
there are no established sanitisation procedures as they
exist for MRSA.” Instead, Hamprecht recommends better
hygiene measures in hospitals and practices, reducing the
intake of antibiotics and more training for doctors.
21
SCIENCE – TRANSLATION IN FOCUS
DZIF ANNUAL REPORT 2015
Achim Hörauf’s DZIF research team (in the photo with patients in Africa) develops an agent for worm infections which are
widespread in Africa.
22
Novel Antiinfectives
Discovering old
treasures anew
Antibiotics constitute one of the biggest successes in the history of medicine. They
have increased human life expectancy and have made infectious diseases less dramatic.
However, pathogens are increasingly developing resistance that render the “wonder
drugs” ineffective. New antibiotics are urgently required. In the research field “Novel
Antiinfectives”, DZIF scientists systematically search for alternative target structures for
antibiotics. They develop new active substance candidates and agents that support our
natural immune defence.
Numerous classes of antibiotics were introduced in the
middle of the last century, but there have hardly been
any new ones in recent years. The quest for substances
with new mechanisms of action is complex, and the
chances of finding them are low. DZIF researchers use
automated screening methods to look for viable
substances in extensive natural compound collections.
In addition to this, they are also involved in research
collaborations between science, public establishments
and the industry. In these product development
partnerships (PDP), DZIF scientists and companies
jointly further develop active substance candidates.
Often these drug candidates have already been known
for a long time.
Rough diamond cut for tuberculosis treatment
Together with scientists from the company Sanofi, DZIF
researchers at the Helmholtz Institute for Pharmaceutical
Research (HIPS), Saarbrücken and the Helmholtz Centre
for Infection Research (HZI) optimised the active agent
griselimycin, previously identified there, for the treatment
of tuberculosis (TB). Tuberculosis treatment entails the
intake of several antibiotics over months. If treatment is
interrupted, resistance to the active substances develops
and the disease exacerbates once again. Griselimycin’s
potential as a tuberculosis drug had already been discovered
in the 1960ies, but its further development was deferred.
“We resumed the work and optimised the parent substance
in such a way that it now demonstrates superb activity,
even against multidrug-resistant tuberculosis pathogens,”
explains Prof Rolf Müller, Head of the HIPS “Microbial
Natural Products” Department and Coordinator of the
“Natural Compound Library” at the DZIF. “The substance
suppresses the activity of DNA polymerase, an enzyme in
the pathogen which is responsible for replicating the cell’s
hereditary information,” explains Müller. Without this
activity the bacteria can no longer reproduce in the body.
This mechanism of action is different to that of previous
tuberculosis agents and the danger of developing resistance
is low, for now.
Versatile natural gem
DZIF scientist Achim Hörauf and his colleagues from the
Bonn University Hospital are also collaborating with the
industry to develop the natural substance corallopyronin.
SCIENCE – TRANSLATION IN FOCUS
Griselimycins are also effective against multidrug-resistant tuberculosis bacteria. The substance (ball and stick model) binds to the
so-called DNA clamp, a protein which is important for bacterial
DNA replication. The bacteria become unable to reproduce due to
this binding (at the top and centre of the image).
Researchers at the HZI had already discovered its efficacy
against Staphylococci in the 1980s. In 2009, Hörauf and
his team confirmed its efficacy against different filarial
worms. If left untreated, infections with these worms can
cause elephantiasis, a condition in which a part of the body
becomes enlarged. Corallopyronin A damages the worms
by attacking their symbiotic partner: “It destroys bacteria
inside the filarial worms without which they are unable to
survive,” explains Hörauf. The active substance blocks the
enzyme RNA polymerase in the bacterial cells, which is
responsible for replicating genetic material and the
bacteria become unable to reproduce. “Currently,
corallopyronin A is undergoing preclinical testing, which
will also be conducted in dogs or minipigs because they
have a similar metabolism to humans,” says Hörauf. “The
investigations could then also be interesting for veterinary
drug manufacturers and be used to treat canine filarial
infections,” Hörauf believes.
The DZIF researchers from Bonn also made another
discovery: “teixobactin”. As members of a team of
international scientists, they uncovered the mechanism of
action of this antibiotic substance which is effective
against a broad spectrum of pathogens. With
“cystobactamides” DZIF colleagues from the HIPS and
HZI even found a new antibiotic substance class which
could also be used to treat gram-negative bacteria.
23
Goals for 2016 at a glance
• Provide initial evidence of antibiotic efficacy of aminochelocardins in preclinical animal model testing.
• Develop a new production and purification protocol for corallopyronin A in preparation for GLP preclinical testing, subsequent to successful efficacy testing.
• Conduct initial “proof of concept” studies for the antiviral activity of selective RIG-I and TLR8 ligands.
Coordinator:
Prof Dr Hans-Georg Sahl
Bonn
DZIF ANNUAL REPORT 2015
Product Development Unit
RESEARCH INFRASTRUCTURES
Support on the long road to
an active agent
Scientists and the Product Development Unit work together closely
to develop a vaccine against MERS.
24
Getting from a molecule to a drug is a tedious and
lengthy task. 95 percent of substances fail as early as
at the laboratory stage. Successful drug development
requires scientific, regulatory and economic knowhow. The DZIF “Product Development Unit” offers
researchers expert advice.
The DZIF Product Development Unit (PDU) is closely
interconnected with the research fields. The PDU
regularly highlights relevant research findings as well
as promising active agent and vaccine candidates,
evaluating those which have realistic chances of being
developed further. “We contribute to accomplishing
the DZIF’s translational research mission by supporting
specific product development research and focusing on
these aspects,” emphasizes Prof Klaus Cichutek who
coordinates the projects at the PDU.
Continuous support from molecule to market entry
Dr Thomas Hesterkamp is a human biologist and
Head of the Translational Project Management Office
(TPMO) at the Helmholtz Center for Infection Research
in Braunschweig. The TPMO is one of two separately
managed PDU departments and provides support
for organisational and commercial matters. “We plan
the further development, provide advice for funding
applications and negotiate contracts with industrial
partners,” says Hesterkamp. The second department is
located at the Paul-Ehrlich-Institut in Langen: the Office
for Scientific and Regulatory Advice (OSRA) advises
on scientific-regulatory matters, also for early stages
of drug discovery. With the Federal Institute for Drugs
and Medical Devices (BfArM) in Bonn, the DZIF has
incorporated a further institute into OSRA. With this, the
PDU covers the entire spectrum of regulatory expertise
for drugs and medical devices. In 2015, BfArM hosted a
series of kick-off meetings and consultations for DZIF
projects.
Vaccine ready for clinical trials
An example of the good collaboration between the
PDU and research at the DZIF is the development of a
vaccine against the “Middle East Respiratory Syndrome
coronavirus” which causes severe respiratory tract disease
in humans. The “MVA-MERS-S vaccine” has already been
confirmed effective in camels, which transmit the virus,
and is now due for clinical testing in humans. Thanks to
the PDU’s continuous support, the vaccine was rapidly
produced in collaboration with a vaccine manufacturer to
serve as trial medication.
Coordinator:
Prof Dr Klaus Cichutek
Langen
Clinical Trial Unit
gates to what extent it is accepted by the vaccinated
person’s immune system,” explains Vassiliki Dimitriou,
CTU Project Manager.
New active agents are tested in the Clinical Trial Unit before they
enter the market.
How do drugs and vaccines affect the body? New
drugs are tested carefully before they are launched
into the market—also on humans. Specialised clinical
trial centres exist for such tests. At the DZIF they
are organised into an independent Clinical Trial Unit
(CTU).
Clinical trials on humans are strictly regulated. Precise
execution and monitoring protocols exist for every single
step. At the CTU, these are subject to comprehensive
quality management that exacts consistently high
standards. Since 2012, the CTU has conducted over 60
clinical trials and 68 feasibility studies. These investigations
are coordinated and managed by the “Coordinating Office”
in Cologne. It is the central point of contact and provides
access to a broad range of scientific expertise.
Prepared for growth
Two new clinical trial centres joined the CTU in 2015.
Now, 11 German establishments of this kind work
together under the umbrella of this network. Additionally,
the CTU is planning to make its own scientific contribution
with a trial that is relevant to the DZIF: “It concerns the
pneumococcal vaccine for dialysis patients and investi-
Catering for internal and external networks
Beyond this, the DZIF infrastructure is also attractive
for external scientific and industrial institutions. Here,
the DZIF centres not only test active agents that have
been developed internally, but also offer this service to
interested clients. This makes the DZIF a strong partner
for global infectious disease networks—for example,
for the American Antibacterial Resistance Leadership
Group (ALRG), which is specialised in clinical research on
antibiotic resistance. Prof Oliver Cornely, Coordinator of
the DZIF Clinical Trial Unit is enthusiastic, “The DZIF is
the only European centre that has been incorporated into
this important network.”
Coordinator:
Prof Dr Oliver Cornely
Köln
RESEARCH INFRASTRUCTURES
Putting agents to the
acid test
25
DZIF ANNUAL REPORT 2015
African Partner Institutions
RESEARCH INFRASTRUCTURES
Collaborating across
the continents
Participants of a clinical Ebola vaccine trial in Lambaréné, Gabon.
26
Infectious diseases like AIDS, tuberculosis, malaria
and Ebola are particularly prevalent in African
countries. DZIF scientists collaborate with “African
Partner Institutions” in order to research these
diseases locally. Some of these collaborations have
been successful for decades.
DZIF scientists at university hospitals and tropical
medicine institutes in Hamburg, Heidelberg, Tübingen and
Munich conduct different research projects in collaboration with African colleagues from renowned scientific establishments in Ghana, Gabon, Burkina Faso and Tanzania.
Valuable on-site contacts
Thanks to collaborations with the African Partner
Institutions, the researchers have the best conditions
at their disposal for conducting their empirical work:
housing, modern laboratories, infrastructures and trained
personnel are available for clinical trials. Owing to many
years of experience, the scientists are familiar with import
and export arrangements for material and samples.
Epidemiological studies recording the temporal and spatial
spread of pathogens in affected regions also constitute a
part of the projects conducted in Africa.
Clinical studies with expert colleagues
The clinical efficacy and dosage trials on the Ebola vaccine
candidate “rVSV-ZEBOV” in Gabon are a success story
arising from these partnerships. “The next Ebola outbreak
is going to emerge although we do not know when and
where. When this happens, we can use this vaccine
because it is the most promising and advanced one we
have,” says Prof Peter Kremsner, Director of the Institute
for Tropical Medicine, Tübingen University. Further
examples of successful collaboration are epidemiological
studies investigating “fever of unknown origin”, which are
being conducted together with all four African partners.
DZIF researchers from the University of Munich and
colleagues from the Bundeswehr Institute of Microbiology
equipped a laboratory in Tanzania with the latest molecular
diagnostics and trained staff on site. “Our Tanzanian
partners have examined over 1,000 patients with fever of
unknown origin in hospitals,” describes Dr Gerhard Dobler
from the Bundeswehr Institute of Microbiology. Besides
malaria, bacterial infections, such as typhoid, were included
in the causes of febrile disease. The researchers were also
able to identify pathogens transmitted by mosquitoes, like
dengue, Rift Valley fever and chikungunya viruses.
Coordinator:
Prof Dr Jürgen May
Hamburg
Natural Compound Library
Efficient mass spectrometry platforms are needed to discover new
natural substances.
At the DZIF’s “Natural Compound Library” substances
from bacteria, fungi and plants are collected, isolated
and characterised. The researchers have a particular
focus on microorganism substances with a high potential of being developed further pharmaceutically.
Recently, the “Natural Compound Library” collection
was expanded significantly—mainly with bacterial agent
collections from other DZIF partner sites. With this,
the number of natural substances has doubled to now
600 natural substances. The aim is to pool and store all
DZIF collections in one location. This ensures that the
substances are stored according to quality standards
at - 80 °C and in specific solvents. They are barcoded
and accessible via robots and available to all DZIF
establishments.
First steps on the road to a drug
Numerous screenings with specific substances have been
conducted in collaboration with the DZIF research fields.
Meanwhile, they are in the “hit-to-lead” phase, i.e. being
assessed for their potential application as drugs. In future,
the scientists are to focus more on small molecules for
developing antiviral drugs.
Good prospects for market launch
In 2015, DZIF scientists were granted important
funding for their discovery of a new substance class,
cystobactamides, from the Innovative Medicines Initiative
(IMI) in the “European Gram-negative Antibacterial
Engine” (ENABLE) project. This is a completely new active
substance class for gram-negative hospital pathogens.
Prof Rolf Müller from the Helmholtz Institute for
Pharmaceutical Research Saarland (HIPS) summarises
his research group’s success: “We are pleased that
cystobactamides are included in the small group of
substances that have been approved for this renowned
drug development programme. Consequently, we have
realistic chances of the substance being developed further
and entering the market.”
RESEARCH INFRASTRUCTURES
Expanding natural substance
collections
27
Coordinator:
Prof Dr Rolf Müller
Braunschweig/Saarbrücken
DZIF ANNUAL REPORT 2015
Biobanking
RESEARCH INFRASTRUCTURES
Collected, documented,
stored
Collection of Microorganisms and Cell Cultures (DSMZ)
in Braunschweig, which contains over 27,000 different
bacterial strains with 600 alone for the DZIF. As of 2016,
the pathogen repository will become an independent
DZIF infrastructure.
DZIF biobank samples are carefully inspected.
28
Cell, tissue and body fluid samples are required for
many studies in infection research. This biomaterial
is stored according to quality standards and
systematically documented in biobanks. The DZIF has
its own “Biobanking” infrastructure where experts
advise DZIF scientists on the selection and use of the
samples.
“We have already supported many DZIF colleagues from
different disciplines in their research projects,” says Prof
Peter Schirmacher, Coordinator of the “Biobanking”
infrastructure. This DZIF establishment has a coordinating
office and a technology platform which have assisted
in pooling both existing and new sample collections.
This is additionally being supported by the central DZIF
biological sample registry and its corresponding software.
In collaboration with the TU Munich, the DSMZ is
establishing a collection of bacteria from mouse gut
flora. The “mouse microbiome” is similar to that of
humans, and serves for research on immune reactions
in the gut. Together with the research field “Infections
of the immunocompromised Host”, a data and sample
collection from transplant patients is being established. A
national transplant cohort will be assembled from this, for
which medical data and biological samples of transplant
patients from throughout Germany can be collected. This
constitutes an important basis for future studies.
National and international networking
Furthermore, the DZIF unit strengthened its networking
with other biobanks: it initiated the biobanking & IT
working group within the German Centers for Health
(DZG) network. Led by DZIF colleagues, it develops
recommendations for more consistency in the DZG’s
activities. “We have standardised procedures for the IT
system, storing samples and quality control,” exemplifies
Prof Schirmacher.
Coordinator:
Prof Dr Peter Schirmacher
Heidelberg
Samples, patient data and pathogens
DZIF Biobanking is coordinated from the partner site
Heidelberg. The DZIF tissue bank which contains a
collection of infected patient samples is located there.
Fluid samples like serum, plasma, urine and saliva are
stored at the Helmholtz Zentrum München. Pathogens
and agent-producing bacteria are stored in the German
Bioinformatics
Participating scientists bring their own tasks from
their daily research work to the seminars, for example,
analysing the microbial species diversity in the
gastrointestinal microbiome. “For instance, the scientists
learn how larger DNA sequences are assembled or how
functional genome analysis and database comparisons
are conducted,” explains Bremges.
The Bioinformatics Metagenomics workshop was in high demand
last year.
An important task of the DZIF infrastructure
“Bioinformatics” is to support scientists in evaluating
and interpreting their infection research data. To
this effect, the bioinformaticians make available
“intuitive” software and analysis pipelines, and
deliver their knowledge through bioinformatics
training seminars and workshops.
Andreas Bremges, Project Manager of “Bioinformatics”
at the Helmholtz Center for Infection Research (HZI)
in Braunschweig, places particular emphasis on the
practical application of seminar contents and ability to
use the software in daily research life. Together with
colleagues, he lays the foundations for this by developing
and testing bioinformatics programmes and installing the
required software onto DZIF servers. All DZIF scientists
can either download and use the software independently
or apply for access to the servers. In order to pool the
services, the Gießen and Braunschweig sites are going to
be merged at the HZI.
Programming for all purposes
The trainings conducted by the bioinformaticians
provide practical basic knowledge for all programmes.
Workshops for internal and external scientists
In 2015, the number of DZIF workshops that take place on
a regular basis was increased and will be expanded further
in future. A 2015 highlight for the DZIF bioinformaticians
was the metagenomics workshop which included
lectures from renowned external experts. The increasing
number of workshop participants underlines the need for
courses like this—also for external researchers and DZIF
Academy stipend holders.
Coordinator:
Prof Dr Alice McHardy
Braunschweig
RESEARCH INFRASTRUCTURES
Software, services and seminars
for infection researchers
29
DZIF ANNUAL REPORT 2015
PROMOTION OF YOUNG RESEARCHERS
DZIF Academy
Excellent support for the
best young talents
stipends” to medical students and doctors who would like
to attain an internationally recognised PhD. The “DZIF
Spring, Summer and Autumn Schools” serve as training and
networking platforms. Special courses, which are jointly
organised and conducted by DZIF experts deliver basic
knowledge in different fields—ranging from bioinformatics
through clinical trials to science communication.
The DZIF Academy offers young doctors and scientists career
opportunities in infection research.
30
The DZIF intensively promotes next-generation
scientists. The DZIF Academy offers specialised training
and career opportunities in infection research to
selected doctors and scientists.
The DZIF Academy coordinates a broad training programme and provides specific support for young mothers
and so-called “clinician scientists”—ranging from medical
students to specialists. The Academy’s selection and
supervision of stipend holders is conducted from the
Technical University of Munich. Funding is available on an
individual basis at the different DZIF partner sites. In 2015
alone, the Academy supported a total of 33 stipend holders
in four different programmes.
Learning from experts
Dr Gabor Dunay is enthusiastic about his career as a
clinician scientist. He completed his PhD with highest
distinctions. Besides his practical experience in internal
medicine, he also brings with him infection research
experience. “HIV research fascinated me,” Dunay says. He
wanted to be involved with HIV cure research at one of the
leading institutes. He was so interested in the molecular
genetic approach pursued by Prof Joachim Hauber and his
team at the Heinrich Pette Institute in Hamburg (HPI) that
he submitted an unsolicited application. A few months later
he started his work as a DZIF stipend holder. With Hauber
and Dr Julian Schulze zur Wiesch, his doctorate supervisor,
both from the University Medical Center HamburgEppendorf, he has two renowned mentors at his side for
his dissertation, and will be one of the first to complete the
MD/PhD programme. He does not want to miss out on
clinical patient work: “I have always wanted to be both a
physician and researcher,” Dunay says determinedly.
Coordinator:
Structured career promotion
The DZIF Academy supports doctors who are interested
in qualifying for a scientific infection research career
with a “Clinical Leave” funding programme. “This is our
most successful programme,” says Cauleen Noël, DZIF
Academy Project Manager. In the “Laboratory Rotation
Programme”, stipend holders gain insight into new methods
and other laboratories. “Maternity leave stipends” facilitate
combining a career and family. The Academy awards “PhD
Prof Dr Ulrike Protzer
München
Collaborations at the DZIF
Viruses are also transmitted from wild birds to humans.
At the DZIF, scientists from research establishments,
university hospitals and specialised federal research
institutions collaborate. Natural scientists, human and
veterinary doctors intensively exchange information
in some of the projects, which is in line with the “One
Health Concept”: infectious diseases equally affect
humans, animals and the environment.
Antibiotic resistance, for example, clearly demonstrates
how closely humans, animals and the environment are
connected: the increased use of antibiotics in animal
feed is responsible for the rise of resistant pathogens,
amongst other things. Furthermore, many emerging
infectious diseases can be ascribed to pathogens that are
transmitted from animals to humans, so-called zoonoses.
Early warning system for new infections in humans
Prof Martin Groschup from the Friedrich-Loeffler-Institut
(FLI) explains this, giving his wild bird monitoring project
as an example: “We investigate samples from crows,
blackbirds and many other birds for evidence of infection
with viruses that are transmissible to humans, for example
viruses which are imported into Germany due to climatic
changes as well as through global trade and change,” the
veterinary doctor explains. “These include flaviviruses
like the West Nile virus and Zika, as well as alphaviruses which cause arthritis and encephalitis, as well as
influenza viruses and numerous different bunyaviruses.”
With their longstanding experience, researchers at the
FLI are able to distinguish between wild birds that have
contracted new viruses and those with older, familiar
viruses which have suddenly developed a higher disease
potential for humans. Consequently, they have developed
a kind of animal “early warning system”. The researchers
collaborate with colleagues from the DZIF research
field “Emerging Infections” so that measures against
new infectious diseases in humans can be implemented
significantly earlier.
Reinforcement for the DZIF
Since June 2015, the DZIF’s expertise has been furthered
by three new member establishments: the FriedrichLoeffler-Institut (FLI), with headquarters on the Baltic
Sea island of Riems, contributes expertise in animal health.
The Robert Koch Institute (RKI) in Berlin is involved with
infectious disease prevention and control measures. The
Federal Institute for Drugs and Medical Devices (BfArM)
in Bonn is responsible for drug approval and regulating
clinical trials. With these institutes, the DZIF has again
expanded its scientific expertise in order to better face
the challenge of global infectious diseases in humans and
animals.
COLLABORATIONS AT THE DZIF
One Health:
humans – animals – environment
31
DZIF ANNUAL REPORT 2015
DZIF Highlights 2015
DZIF HIGHLIGHTS 2015
DZIF news
January
DZIF scientists are involved in the
discovery of two
novel antibiotics. Teixobactin seems
promising for gram-positive
bacteria and cystobactamides may
soon stand up to gram-negative
bacteria.
May
Together with the company Hyglos,
scientists from the Universities of
Tübingen, Münster and Munich join forces
at the DZIF to prepare the clinical trial of
an agent against the dreaded hospital
pathogen Staphylococcus aureus: a
highly effective bacteriophage
protein is to kill the bacteria
within the shortest time.
32
February
At a joint dinner debate in
Berlin on 2 February, the
DZG illustrate how they intend
to accelerate the translation of
research findings into clinical
practice.
March
Virologists at the
Heinrich-Pette-Institut in
Hamburg have developed a
mouse model for Ebola
research with which Ebola
infections can be better
investigated.
April
Clinical phase I trials on a potential vaccine
against the dreaded Ebola virus were completed
successfully at four partner sites in Africa and Europe.
Conclusion: the preliminary tolerability and safety
results, as well as the immune response to the vaccine
candidate are promising.
An international team of researchers including
scientists from the DZIF and the University Hospital
Cologne has tested a new generation of antibodies
in humans for the first time, and showed that
these broadly neutralising antibodies
significantly reduce the viral load of
patients with HIV infection.
June
The DZIF is growing: three new
member establishments will be
supporting the DZIF’s research activities in
future—the Friedrich-Loeffler-Institut (FLI),
the Robert Koch Institute (RKI) and the Federal
Institute for Drugs and Medical Devices
(BfArM).
The DZIF is highly involved in one of five new
African-German research networks. The
BMBF supports tuberculosis research
in a project running under name
“TB-Sequel”.
A new training programme for
clinical infectious disease specialists is initiated on 1 July. It is probably
the first of its kind in Germany. At the
northern-most DZIF partner site
Hamburg-Lübeck-Borstel, clinical
infectious disease specialists are
now jointly being trained across
the federal states.
August
September/
October
With an unusual treatment method,
doctors from the Hannover Medical
School (MHH) succeed in curing a patient
with life-threatening diarrhoeal disease:
they transplanted another person’s faeces
into his gut which displaced the disease
pathogens. Faecal transplants are
currently being researched
extensively at the DZIF.
DZIF HIGHLIGHTS 2015
July
33
An international scientific review
committee certifies “major advances” in
an evaluation of the DZIF’s activities
since it was founded in 2012.
Following this positive evaluation
the DZIF confidently enters its
second round.
December
November
For the first time, the German Society
of Infectious Diseases (DGI) and the German Center for Infection Research (DZIF)
hold a joint Annual Meeting in Munich. On
this occasion, Markus Gerhard, TU Munich,
was awarded the DZIF Prize for Translational Infection Research Prize for
his work on the development of a
vaccine against Helicobacter
pylori.
A German-Dutch team of researchers
successfully vaccinates dromedaries
against the MERS coronavirus. They
are believed to transmit this infectious
disease to humans. In a clinical phase I
trial, the vaccine candidate will also
be tested in humans for the first
time.
SCIENCE AND PUBLIC
DZIF ANNUAL REPORT 2015
What have we learnt from the Ebola epidemic? This topic was discussed at the joint DZIF and DGI Annual Meeting.
34
Science and Public
Making research and development
transparent
2015 was an exciting year for the DZIF in many respects. The development of Ebola and
MERS virus vaccines was advanced rapidly, new potential antibiotics were discovered,
and improved treatment options for HIV and tuberculosis were tested. The Press Office
accompanied these and other promising developments, and made information on them
available to the public. In the era of Ebola, Zika, MERS, hospital pathogens and multidrug
resistance, providing timely and extensive media information on ongoing projects has
become more important than ever.
Infectious diseases again constituted some of the top
media stories. In addition to the above mentioned
emerging infections, new findings on other infectious
diseases researched at the DZIF, such as tuberculosis,
malaria, HIV, hepatitis and gastrointestinal diseases, were
also met with great interest. The DZIF published at least
three press releases a month in 2015.
DZIF supports the Science Media Center Germany
Reporting on medical issues is often challenging.
Journalists require rapid and correct information,
especially in events of sudden infectious disease
outbreaks like Ebola and Zika. Who can provide reliable
information on a topic; who has the necessary expertise?
The DZIF Press Office is always available to assist in
finding experts, and is actively supported in this venture
by many dedicated DZIF scientists.
The Science Media Center (SMC) was recently
established in Germany. It is based on a British model
aiming at delivering high quality scientific reporting. As
soon as scientific topics make the news, the SMC provides
interested journalists with reliable, expert information,
statements and analyses. In order to ensure timely
reporting, it first established an expert database. The
Press Office motivated many DZIF scientists to actively
participate and provide the centre with information on
infection research topics.
The DZIF as one of six German Centres for Health
Research
The DZIF’s focus is on collaboration. Together with the
five other German Centers for Health Research (DZG),
it publicly discusses its task of research translation. The
DZG organised a 2015 World Health Summit workshop,
led by the DZIF, in which speakers from the DZG and
international guests participated. The topic of discussion
was strategic education and training of clinical and
translational scientists and the tools used to achieve this
in other European countries and the USA. The DZG will
also be holding a joint workshop titled “Big Data” at the
WHS this year.
An additional form of collaboration amongst the DZG has
been initiated: the BMBF Newsletter “Current Health
Research Findings”, which includes contributions from
about 1,500 editorial offices and/or journalists, has
regularly been reporting on DZG topics since 2015. The
DZIF has contributed with reports on the Ebola vaccine
and Helicobacter pylori research. A joint DZG research
magazine is being planned.
The DZIF is visible: online and at conferences
Besides media work and networking, continuously
developing the DZIF website plays a key role in the DZIF’s
The DZIF lives on information exchange
Germany-wide networking as it exists at the DZIF can
only function with successful internal communication.
The Press Office supports this internal communication
with a quarterly newsletter and via the DZIF intranet, an
exchange platform equally accessible to everyone.
The Annual Meeting, which was held jointly with the
German Society of Infectious Diseases (DGI) for the
first time in 2015, also serves as a professional and
personal exchange platform. Around 400 scientists and
doctors came to Munich and enjoyed both the scientific
discussions and typical Bavarian ambience in the Paulaner
am Nockherberg.
Last but not least, the Press Office also brings out the
Annual Report you are now holding in your hands. With
selected examples, it highlights DZIF activities from the
past year to interested people and funders. A joint piece
of work with many contributions from dedicated DZIF
people. We thank all those involved.
Press and Public Relations:
Karola Neubert
Janna Schmidt
Braunschweig
SCIENCE AND PUBLIC
The new DZIF exhibition stand makes our Translation City visible
beyond German borders.
public presentation. Since 2015, companies, journalists
and scientists can obtain relevant information more easily
through personalised website access. In 2015, around
40,000 people used this service to visit the website.
Besides its virtual presence, the DZIF is increasingly
attending events and conferences to network and connect
with potential partners. Information stands at the ICAAC
in San Diego and the ECCMID in Copenhagen contributed
to making the DZIF visible beyond German borders.
35
COLLABORATIONS
DZIF ANNUAL REPORT 2015
Scientists and industry representatives discussing intensively at the Annual General Meeting.
36
Collaborations with scientific institutions and industry
External
collaborations
Numerous associated partnerships and other external collaborations reinforce the DZIF’s
position as a top-class institution in the field of infection research.
DZIF’s associated partners
University of Freiburg
Current problems with tuberculosis diagnostics are being
researched in a project with the University of Freiburg.
One aspect of the project is establishing a novel diagnostic
testing system (TB-Disk) for detecting resistance in
clinical isolates. In Freiburg, a so-called Lab-on-a-DiskSystem is being developed and will be validated at the
African Partner Institutions.
Charité – Universitätsmedizin Berlin
Die Charité – Universitätsmedizin Berlin is partner in
a study on the intelligent use of antibiotics (ATHOS:
antibiotic therapy optimisation study). It investigates
whether interventions for targeted antibiotic use in
hospitals (antibiotic stewardship, see University Medical
Center Freiburg) and in practices (Charité) influence the
number of new cases of infection with certain antibioticresistant bacteria. A method which was developed in the
new module „ATHOS-MRE-Surveillance“ at the Charité is
German Liver Foundation/HepNet Study House,
Hannover
The HepNet Study House networks trial centres for
hepatitis research, and provides a platform for conducting
clinical trials. The DZIF can use the infrastructures and
cohorts for its projects. Current research activities focus
on hepatitis B, C, D and E. Together with the German
Liver Foundation, a global registry of patient with chronic
hepatitis D was established (www.hepatitis-delta.org)
which is to be updated continuously. Over 800 patients
were registered by the end of 2015.
Friedrich-Loeffler-Institut, Riems
(DZIF member since June 2015)
The Friedrich-Löffler-Institut (FLI) is partner in a
collaborative project aimed at the early detection of
pathogens, particularly those transmitted by animals. The
FLI provides the necessary blood and tissue samples, as
well as nucleic acid preparations, from both domestic and
wild animals. Especially the unique European laboratory
and animal testing facilities, with biosafety levels 2 to 4,
make the FLI an important partner for the DZIF.
Gottfried Wilhelm Leibniz Universität Hannover
DZIF scientists recently discovered a completely new
substance class called cystobactamides, which is effective
against difficult-to-treat gram-negative bacteria. A
project at the HZI is to develop these cystobactamides
further, so that they can undergo testing as potential
antibiotics in preclinical trials. Scientists at the Leibniz
Universität Hannover succeeded in conducting the first
total synthesis of cystobactamide C, which paves the way
to the synthesis of further cystobactamide variations.
Goethe University Frankfurt am Main
A project focusing on hepatitis, in which clinical cohorts
are being established, is currently ongoing at the Goethe
University Frankfurt am Main. Blood samples, taken from
patients with chronic hepatitis C are taken before therapy
or after therapy failure, are available to all collaborating
partners. The clinical data, along with viral and host gene
analysis and phenotypic results, are analysed and recorded
in an online-based tool. This tool aims at improving the
evaluations of courses of disease and treatment responses,
and to tailor individual treatment (see MPI for Informatics).
In a second project with the University Hospital Frankfurt,
multidrug-resistant Enterobacteriaceae, which spread very
easily and constitute an increasing problem in hospitals, are
being investigated more closely. Up to now, it is not known
why certain strains of bacteria are much more successful
than others.
Hans Knöll Institute, Jena
The Hans Knöll Institute (HKI) is a leading institute for
natural compound research. As an associated partner,
it provides the DZIF with natural compounds, especially
fungi. A project is investigating the pharmacodynamics
of corallopyronin A, a natural product that has already
been successfully tested against the filariasis pathogen
and is undergoing preclinical evaluations. The HKI is
largely responsible for its biosynthesis. In a further joint
project, the DZIF will advance the development of a new,
promising agent against tuberculosis from the HKI, which
has already undergone preclinical testing.
Max Planck Institute for Informatics, Saarbrücken
At the Max Planck Institute for Informatics in
Saarbrücken, data on hepatitis C patients who are
undergoing treatment with new antiviral agents is being
collected as part of a DZIF project. Sequencing, analysis
and interpretation of patient and viral genes, along with
other parameters, will be used to evaluate the course of
treatment. In Saarbrücken, the analysis results are being
used to further develop an online-based tool, the socalled Geno2pheno[HCV]. The analysis results are freely
accessible online, and can be used to support decisions for
personalised treatment.
Robert Koch Institute, Berlin
(DZIF member since June 2015)
The DZIF and the Robert Koch Institute (RKI) collaborate
in many areas. A few examples: In the research field
“Emerging Infections”, the RKI supports strategic
partnerships between research establishments, hospitals
and pharmaceutical companies. In clinical trials, clinical
guidelines are being developed jointly. The DZIF has
access to the RKI’s new databank “HIOBs” for its HIV
research; the software was optimised and, after it proved
to be successful in Cologne and Hamburg, it is now being
implemented at the partner sites.
RWTH Aachen University
The RWTH Aachen University Medical Center is
partner and trial centre for a “Healthcare-associated
COLLABORATIONS
being used to monitor the multidrug-resistant organisms.
In 2015, the distribution of patient information material
to practice-based doctors in Berlin was completed.
Additionally, data from all participating centres collected
in Berlin were analysed.
37
DZIF ANNUAL REPORT 2015
COLLABORATIONS
and Antibiotic-resistant bacterial Infections” research
field project. In two multicentre studies, the clinical
effectiveness for measures against multidrug-resistant
Enterobacteraiceae is being tested on cancer patients.
While the first study is investigating the impact of
antibiotics on colonisation, the second study will observe
whether isolating the affected patients can stop the
spread of the pathogen.
38
University Medical Center Freiburg
In a project with the University Medical Center Freiburg
investigating infections of the immunocompromised host,
scientists are looking to find genetic factors associated
with increased susceptibility to infection, particularly
fungal infections. They intend to find biomarkers that
permit better infection control.
A second DZIF project is investigating the more targeted
use of antibiotics (see also Charité). The University
Medical Center Freiburg is participating in the ATHOS
study for which it is recording the colonisation of patients
with certain multidrug-resistant bacteria. They are also
investigating Clostridium difficile associated diarrhoea.
University of Münster
The University of Münster is partner in a project
aimed at developing new treatment strategies against
gastrointestinal infections. In many cases, the commonly
used antibiotics harm the normal gut flora and can lead to
complications. In Münster, the scientists are working on
preventing the complications associated with EHEC. They
have obtained economical pectin derivatives which could
inhibit bacterial toxins.
A second project is working on hospital pathogens,
specifically with multidrug-resistant Staphylococcus
aureus in the nasal region. Here, new lytic phage proteins
for targeted treatment are being investigated. Their
efficiency and specificity will be analysed in Münster.
Industry collaborations
Hyglos GmbH, Bernried
Hyglos GmbH and a consortium funded by the DZIF are
collaborating to manufacture and preclinically develop
phage lytic protein HY-133 (see University of Münster).
They are planning joint early-stage clinical development
for nasal decolonisation of Staphylococcus aureus.
ImevaX GmbH, Munich
The DZIF is funding a research group led by Prof Markus
Gerhard from the Technical University of Munich in the
field of preclinical and early-stage clinical testing of the
Helicobacter pylori vaccine candidate IMX-101. Together
with other funders, the group founded a spin-off company
from the university, ImevaX GmbH.
Juno Therapeutics GmbH, Göttingen
Juno Therapeutics, formerly Stage Cell Therapeutics,
is collaborating and exploitation partner of the research
group led by Prof Dirk Busch, Technical University of
Munich, working in the field of GMP quality-assured
manufacture of central memory T cells for treatment of
infections and cancer. The DZIF is funding the group led
by Prof Busch.
MMV – Medicines for Malaria Venture, Geneva
(Switzerland)
An MMV portfolio substance is being clinically tested
for chemoprevention of malaria tropica, using a human
infection model developed by DZIF colleagues in
Tübingen.
Myr GmbH, Burgwedel
Together with the University of Heidelberg, an active agent
(Myrcludex B) is being developed that inhibits hepatitis B
viruses from penetrating cells, and could potentially be
used to prevent hepatitis B and D infections. Myr GmbH is
coordinating the entire project and overseeing the clinical
trial.
Sanaria Inc., Rockville (USA)
At the DZIF partner site Tübingen, scientists are developing a human malaria infection model. Here, the disease
is induced under controlled conditions in order to test
new active agents and vaccines. Sanaria Inc. in Rockville,
USA, produces malaria parasites in GMP quality for
immunisation purposes, which fulfil all the criteria for drug
approval.
4SC Discovery GmbH, Martinsried
In the DZIF research field “Malaria”, a candidate antimalarial has gone into preclinical development. SC83288
is being tested as an inhibitor in animal models, and is
being further developed in close collaboration with the
company 4SC, which also produces the active agent.
DZG
2009 already saw the foundation of the “German Centre
for Neurodegenerative Diseases” and the “German
Centre for Diabetes Research”. Alongside the DZIF,
the “German Center for Cardiovascular Research”, the
“German Consortium for Translational Cancer Research”
and the “German Center for Lung Research” launched in
2012.
From the outset, the six German Health Research Centres
have collaborated closely in order to share their findings
and exploit synergies.
DZG
German Health Research
Centres
The German Health Research Centres‘ goal is translation. Research
findings are to reach the patient more rapidly.
The main objective of the German government‘s
health research programme is to develop more
effective ways to combat widespread diseases. The
groundwork for this has been laid on federal and state
levels with the establishment of German Health
Research Centres (DZG) as long-term, equal partnerships between non-university research institutes and
universities with medical centres.
These German Health Research Centres pool all of
their existing expertise, thereby greatly helping to close
knowledge gaps and improve prevention, diagnosis and
therapy of the respective diseases. The research policy
ensures close collaboration between basic research and
clinical research, always specifically aligned with the
indications and the patients’ needs. Close networking and
the expansion of existing research structures will allow
faster transfer of research results into clinical practice
(translation).
The strategic cooperation of leading scientists in the
German Health Research Centres promotes Germany
to a high-ranking scientific location and increases its
attractiveness to young scientists in Germany and around
the world.
39
DZIF ANNUAL REPORT 2015
Organisation and bodies
Structure of the DZIF
General Assembly
FACTS AND FIGURES
The General Assembly is the central decision-making organ of the DZIF and comprises representatives of the DZIF member establishments. The General Assembly elects the Executive Board members and the Executive Director, and decides on the allocation of funds to
the research fields and infrastructures (TTUs and TIs).
Commission of Funding Authorities
Executive Board
Scientific Advisory Board
The Commission of Funding Authorities is
made up of the Federal Government and
respective states (Länder) and decides on
important matters of finance, organisation and personnel. The Executive Board
and the Managing Director report to the
Commission on all funding measures.
The Executive Board represents the
DZIF externally. It implements the
resolutions and tasks assigned by the
General Assembly and is responsible for
routine administrative affairs.
The association is supported by the
Scientific Advisory Board, consisting of
internationally renowned experts from
the field of infection research. The Scientific Advisory Board advises the Executive
Board and General Assembly on all
scientific and programme-related matters.
Main Office
Internal Advisory Board
The members of the Internal Council are
DZIF scientists representing all research
fields and locations of the centre.
The council advises the Executive Board
on all scientific, programme-related
and technical matters and performs
representative duties.
The Main Office is located in Braunschweig and supports the Executive
Board in its work. Its duties include
organising research initiatives and
coordinating DZIF’s press and public
relations activities.
40
Thematic Translational Units (TTUs)
Translational Infrastructures (TIs)
The Thematic Translational Units pool the DZIF‘s research activities.
Each unit is dedicated to one pathogen or to one specific problem in
infection research.
Strategically aligned translational infection research requires
modern infrastructures. These are provided in the form of the
Translational Infrastructures, and can be used by all DZIF members.
Emerging Infections
Tuberculosis
Product Development Unit
Biobanking
Malaria
HIV
African Partner Institutions
Bioinformatics
Hepatitis
Gastrointestinal Infections
Natural Compound Library
Infections of the immunocompromised Host
Healthcare-associated and
Antibiotic-resistant bacterial
Infections
DZIF Academy
Novel Antiinfectives
Clinical Trial Unit
Pathogen Repository
(since 2016)
Epidemiology (since 2016)
Partner Sites
DZIF conducts its research in 35 research establishments at seven locations throughout Germany. At each site, two scientists are appointed to coordinate the collaboration and to advise the Main Office. Various external research partners are also involved in DZIF projects.
Bonn-Cologne
Gießen-Marburg-Langen
Hamburg-Lübeck-Borstel
Hannover-Braunschweig
Heidelberg
Munich
Tübingen
Associated Partners
Central bodies
Executive Board
> Prof Dr M. Krönke, Universität und Universitäts klinikum Köln (Chair)
> Prof Dr U. Protzer, Technische Universität München
und Helmholtz Zentrum München (Vice Chair)
> Prof Dr D. Heinz, Helmholtz-Zentrum für Infektions forschung, Braunschweig
Managing Director
> Dr T. Jäger, DZIF e.V.
Scientific Advisory Board
> Prof Dr P. Alonso, WHO Global Malaria Programme, Switzerland
> Prof Dr R. Burger, Robert Koch Institut, Germany
> Prof Dr H. Feldmann, National Institute of Allergy
and Infectious Diseases, USA
> Prof Dr B. B. Finlay, University of British Columbia,
Canada
> Prof Dr A. Friedrich, Universitair Medisch Centrum
Groningen, Netherlands
> Prof Dr B. Kampmann (Chair), Imperial College London,
United Kingdom
> Prof Dr J.-M. Pawlotsky, Université de Paris XII, France
> Prof Dr C. Rooney, Baylor College of Medicine, USA
> Prof Dr H. J. Schmitt, Johannes Gutenberg-Universität
Mainz, Germany, and Pfizer Vaccines, France
> Prof Dr A. Telenti, The J. Craig Venter Institute, USA
> Prof Dr S. Ward, Liverpool School of Tropical Medicine,
United Kingdom
> Prof Dr R. G. Werner, Universität Tübingen, Germany
Internal Advisory Board
> Prof Dr I. Autenrieth, Universität und
Universitätsklinikum Tübingen
> Prof Dr K. Cichutek, Paul-Ehrlich-Institut, Langen
> Prof Dr C. Drosten, Universität und
Universitätsklinikum Bonn
> Prof Dr M. Hoelscher, Ludwigs-Maximilians Universität München and Klinikum der Universität
München
> Prof Dr R. Horstmann, Bernhard-Nocht-Institut
für Tropenmedizin, Hamburg (Vice Chair)
> Prof Dr H.-G. Kräusslich, Universität und
Universitätsklinikum Heidelberg (Chair)
> Prof Dr T. Schulz, Medizinische Hochschule
Hannover
> Prof Dr T. Welte, Medizinische Hochschule
Hannover
Partner sites and member establishments
Hamburg - Lübeck - Borstel
Hannover - Braunschweig
Bonn - Cologne
Gießen - Marburg - Langen
Heidelberg
Tübingen
Munich
DZIF ANNUAL REPORT 2015
Partner sites and member establishments
FACTS AND FIGURES
Germany-wide
infection research
43
Baden-Württemberg
Heidelberg is responsible for coordinating the TTU HIV at the DZIF. In
order to control HIV infections,
DZIF researchers at this location
research factors of the innate
immune system and identify DNA
sites for viral DNA integration.
Alongside HIV, Heidelberg cocoordinates the TTUs Hepatitis,
Malaria and Infections of the Immunocompromised Host. The Heidelberg
scientists also coordinate the DZIFwide translational infrastructure
Biobanking, with a focus on establishing tissue banks.
Heidelberg
Spokesperson: Klaus Heeg (Heidel-
berg University Hospital)
Establishments: German Cancer
Research Center in the Helmholtz
Association, Heidelberg University,
Heidelberg University Hospital
TTU coordination:
• Hepatitis (co-coordination)
• HIV (coordination)
• Infections of the Immunocompromised Host (co-coordination)
• Malaria (co-coordination)
TI coordination:
• Biobanking (coordination)
Tübingen has taken over the
coordinating role at the DZIF for
Malaria and Healthcare-associated
and Antibiotic-resistant bacterial
Infections. Co-coordinators of Gastrointestinal Infections and Novel
Antiinfectives work at this location.
The main focus in Tübingen is on
translating research results into
medicine and vaccine development
as well as on infection models and
epidemiology. Regarding infections
caused by antibiotic-resistant, bacterial pathogens, the focus is on
improving diagnosis and therapy of
multiresistant pathogens such as
methicillin-resistant Staphylococci
(MRSA) and multiresistant gramnegative pathogens (e.g. so-called
ESBLs).
Tübingen
Spokesperson: Prof Ingo Autenrieth
(University of Tübingen)
Establishments: University of
Tübingen, Max Planck Institute for
Developmental Biology, University
Hospital Tübingen
TTU coordination:
• Gastrointestinal Infections
(co-coordination)
• Healthcare-associated and
Antibiotic-resistant bacterial
Infections (coordination)
• Malaria (coordination)
• Novel Antiinfectives
(co-coordination)
Bavaria
Hamburg/Schleswig-Holstein
At the DZIF establishments in
Munich, scientists have a special
focus on immune control of infections and developing novel therapies.
Pathogen-specific immunotherapies
(prophylactic or therapeutic) aim
at strengthening the body’s natural
defence system so that it can control specific infectious diseases more
effectively or even avoid them entirely. Other focuses in Munich are Gastrointestinal Infections, HIV, Hepatitis
and Tuberculosis.
The Hamburg-Lübeck-Borstel site
combines a unique collection of expertise and infrastructure for studying
infectious diseases and emerging
infections of national and worldwide
relevance. It is involved in clinical,
entomological and virological studies.
It is the DZIF base for medical chemistry, for active agent development
as well as for the epidemiology of
malaria and translational studies on
tuberculosis and hepatitis. The TI
African Partner Institutions is coordinated from here.
Munich
Spokesperson: Prof Dirk Busch
(Technische Universität München)
Establishments: Helmholtz Zentrum München – German Research
Center for Environmental Health,
Bundeswehr Institute of Microbiology, Klinikum der Universität München, Klinikum rechts der Isar der
Technischen Universität München,
Ludwig-Maximilians-Universität
München, Technische Universität
München
TTU coordination:
•Gastrointestinal Infections
(co-coordination)
•Hepatitis (co-coordination)
•HIV (co-coordination)
•Infections of the Immunocom-
promised Host (coordination)
• Tuberculosis (co-coordination)
TI coordination:
• Biobanking (co-coordination)
• DZIF Academy (coordination)
Hamburg - Lübeck - Borstel
Spokesperson: Prof Rolf Horstmann
(Bernhard Nocht Institute for
Tropical Medicine)
Establishments: Bernhard Nocht
Institute for Tropical Medicine in the
Leibniz Association, Research
Center Borstel – Leibniz-Center for
Medicine and Biosciences, FriedrichLoeffler-Institut (member since June
2015), Heinrich Pette Institute –
Leibniz Institute for Experimental
Virology, Universität Hamburg,
University Medical Center HamburgEppendorf, Universität zu Lübeck
TTU coordination:
•Emerging Infections
(co-coordination)
•Malaria (co-coordination)
• Tuberculosis (coordination)
TI coordination:
•African Partner Institutions
(coordination)
Lower Saxony
North Rhine-Westphalia
In Gießen-Marburg-Langen, DZIF
researchers identify new active
agents and vaccines and produce
them in quality-assured production
processes for scientific and industrial partners. Research activities
are concentrated on developing
strategies for combatting new or
re-emerging infectious diseases in
order to contain outbreaks of
new pathogens, for example through
quick, effective action and rapid
vaccine development Marburg
focuses on viral pathogens, while
Gießen concentrates on bacteria
and antibiotic resistance.
Seven partner institutes collaborate
within DZIF at the Hannover-Braunschweig location. The TTUs Hepatitis
and Gastrointestinal Infections are coordinated from here. The scientists
here want, among other things, to
improve access to hepatitis therapies and conduct research on new
diagnostic markers for courses of infection and therapy. The researchers
also focus on new pathogen-specific
medicines against pathogens such as
EHEC, Helicobacter pylori or salmonellae. This location coordinates the
establishment of the Natural Compound Library, which is available to all
DZIF researchers in the search for
new medicines.
Bonn-Cologne coordinates the
TTU Novel Antiinfectives. The DZIF
researchers are also researching into
faster and more efficient methods
for characterising unknown viral
pathogens. Unique in Germany are
the patient cohorts for HIV and
HCV infections as well as for HIV/
HCV co-infections. In HIV research,
researchers bring gene-therapy–
based strategies into translation, in
order to control and prevent these
infections. This location coordinates
the DZIF Clinical Trial Unit.
Gießen - Marburg - Langen
Spokesperson: Prof Trinad
Chakraborty (Giessen University)
Establishments: Giessen University, Paul Ehrlich Institute Langen,
Philipps-Universität Marburg,
Mittelhessen University of Applied
Sciences
TTU coordination:
• Emerging Infections (coordination)
• Healthcare-associated and Anti-
biotic-resistant bacterial Infections (co-coordination)
TI coordination:
•Product Development Unit
(coordination)
Hannover - Braunschweig
Spokesperson: Prof Sebastian
Suerbaum (Hannover Medical School)
Establishments: Helmholtz Centre
for Infection Research, Braunschweig,
Leibniz Institute DSMZ – German
Collection of Microorganisms and Cell
Cultures, Hannover Medical School,
Robert Koch Institute (Member since
June 2015) University of Veterinary
Medicine Hannover, Foundation,
Technische Universität Braunschweig,
TWINCORE – Centre for Experimental and Clinical Infection Research
TTU coordination:
• Gastrointestinal Infections
(coordination)
• Hepatitis (coordination)
• Infections of the Immunocom promised Host (co-coordination)
TI coordination:
• Natural Compound Library
(coordination)
• Bioinformatics (coordination)
Bonn - Cologne
Spokesperson: Prof Achim
Hörauf (University of Bonn)
Establishments: Federal Institute
for Drugs and Medical Devices
(BfArM/ Member since June 2015),
University of Bonn, University Hospital Bonn, University of Cologne,
University Hospital Cologne
TTU coordination:
• Emerging Infections
(co-coordination)
• HIV (co-coordination)
• Healthcare-associated and Anti-
biotic-resistant bacterial
Infections (co-coordination)
•Novel Antiinfectives (coordination)
TI coordination:
• Clinical Trial Units (coordination)
FACTS AND FIGURES
Hessen
45
DZIF ANNUAL REPORT 2015
Finance
DZIF financial data 2015
Reported expenditure in euros
FACTS AND FIGURES
By partner site
Associated Partners
1,325,731
Hannover-Braunschweig
Gießen-Marburg-Langen
6,608,705
2,048,728
Heidelberg
3,872,780
Total:
32,137,128
Hamburg-Lübeck-Borstel
4,330,775
Munich
5,568,685
Bonn-Cologne
46
4,129,515
Tübingen
4,252,208
By type of expenditure
Material Expenses
9,187,960
Investments
1,180,769
Total:
32,137,128
Personnel
21,768,400
Field of work
By funders
Euro
Funder
Euro
Emerging Infections
3,184,771
Baden-Württemberg
812,499
Tuberculosis
2,006,193
Bavaria
551,184
Malaria
2,771,930
Hamburg
261,221
HIV
2,571,939
Hessen
145,676
Hepatitis
2,416,503
Lower Saxony
660,871
Gastrointestinal Infections
1,676,355
North Rhine-Westphalia
412,952
Infections in the immunocompromised
Host
3,786,779
Schleswig-Holstein
171,856
Financial contributions from
associated partners
116,109
Healthcare-associated and Antibioticresistant bacterial Infections
2,007,752
Novel Antiinfectives
3,620,723
Product Development Unit
798,009
Clinical Trial Unit
525,680
African Partner Institutions
535,305
Biobanking
814,883
Natural Compound Library
889,107
Bioinformatics
631,488
DZIF Academy
2,071,441
Administration
1,828,270
Total
32,137,128
In 2015, The German Center for Infection Research‘s
reported expenditure was around 32.1 million Euros.
144 projects and 87 stipends were funded within DZIF
in 2015. The majority of funding came from the Federal
Government (90 %) and from Länder funds (10 %). Only
departmental research projects of the federal R&D
institutions were fully funded by Germany‘s Federal
Ministries. Funding management at the Helmholtz Centre
for Infection Research in Braunschweig transfers the
federal funds to the DZIF partner institutes for their
projects.
The expenditures amounting to the BMBF funds were
reported by the DZIF partner in the interim and final
financial report 2015 and will be investigated by the DZIF
funds management. State and associated partner funding
amounts were calculated on the basis of these interim and
final financial reports.
Federal Government
29,004,762
Total
32,137,128
FACTS AND FIGURES
By field of work
47
DZIF ANNUAL REPORT 2015
Personnel and awards
Employees of the DZIF
Full-time equivalent by professional group
Professor
Junior Group Head
FACTS AND FIGURES
10,5
13,3
Physician
Other
25,3
79,9
Total: 351,2
Postdoc
100,4
TA/Study Nurse
75,3
PhD/MD Student
46,5
48
Number of employees by professional group and gender
Professional Groups
Men
Women
Total
Professor
8
4
12
Junior Group Head
13
4
17
Physician
20
26
46
Postdoc
66
125
191
PhD/MD Student
56
63
119
TA/Study Nurse
30
93
123
Other*
41
84
125
234
399
633
Total
*Scientific project manager, data manager etc.
In 2015, the DZIF
recruited six employees
from abroad and assisted
20 mothers on their return
from maternity leave.
Laureates
Awards
Prof Ralf Bartenschlager
Heidelberg University
Robert Koch Award
Prof Petra Gastmeier
Charité – Universitätsmedizin Berlin
Award for Hospital Hygiene and Infection Prevention
Prof Markus Gerhard
Technische Universität München
DZIF Prize for Translational Infection Research
Dr Dr Stephan Göttig
Goethe University Frankfurt am Main
DGHM-Förderpreis
Prof Rolf W. Hartmann
Helmholtz Centre for Infection Research
Carl Mannich-Medaille and
PHOENIX Pharmazie Wissenschaftspreis für
Pharmazeutische Chemie
Prof Achim Hörauf and team
University of Bonn
Memento-Forschungspreis and
Innovationspreis der Bioregionen in Deutschland
Dr Sandra Junglen
University of Bonn
Richard M. Elliot Memorial Award
Dr Benno Kreuels
University Medical Center Hamburg-Eppendorf
Dr. Martini-Preis
Dr Marina Lusic
Heidelberg University
Hector Research Prize
Dr Julia Pagel
Universität zu Lübeck
Heinrich-Finkelstein-Preis
PD Dr Dr Angelika Riemer
Heidelberg University
Ingrid zu Solms-Wissenschaftspreis für Medizin
Dr Julian Schulze zur Wiesch
University Medical Center Hamburg-Eppendorf
Clausthal-Zellerfeld Award
FACTS AND FIGURES
Awards and commendations
49
DZIF ANNUAL REPORT 2015
Indicators 2015
INDICATORS
The DZIF in Figures
FLEXFUNDS*
Number of new
FlexFunds projects in 2015
35
50
Clinical Leave Stipends
22
MD/PhD Stipends
euros
corresponding to
19
WORKSHOPS AND
SYMPOSIA
16
with a budget
of 6,086,624 euros
6,086,624
DZIF ACADEMY
PROGRAMMES
%
of the annual DZIF budget
*funds available at short notice
for translational projects
7
Maternity Leave
Stipends
6
MD Stipends
PUBLICATIONS 2015
WITH
DZIF AFFILIATIONS
276
58
PUBLICATIONS WITH
IMPACT FACTOR >10
Lab Rotations
42
4
647
BIOBANKS
31
PRESS
RELEASES
INDICATORS
CONFERENCE
CONTRIBUTIONS
43
51
PATENTS AND
PROPERTY RIGHTS
21
CLINICAL
STUDIES
25
CONFIRMATORY
PRECLINICAL
STUDIES
WEBSITE
VISITORS
39.515
18
INDUSTRY
COLLABORATIONS
7
DZIF EXHIBITION
BOOTHS AT
CONVENTIONS
COHORTS
21
4
DZIF ANNUAL REPORT 2015
Publications
Scientific achievements
2015
PUBLICATIONS
The following shows a list of selected 2015 publications (impact factor greater than ten).
Please see our website for a complete list of DZIF publications.
52
Basic Research
N, Herrmann J, Wenzel SC, König C,
Jones M, Lazarides L, Steadman VA,
Ammerman NC, Barrio MB, Borchers K,
Cohen DR, Felix CR, Fetterman KA,
1. Amort M, Nachbauer B, Tuzlak S,
Bordon-Pallier F, Brönstrup M,
Millett WP, Nitti AG, Zullo AM, Chen
Kieser A, Schepers A, Villunger A, Polacek
Courtemanche G, Gerlitz M, Geslin M,
C, Lewis K (2015) A new antibiotic kills
N (2015) Expression of the vault RNA
Hammann P, Heinz DW, Hoffmann H,
pathogens without detectable resistance.
protects cells from undergoing apoptosis.
Klieber S, Kohlmann M, Kurz M, Lair C,
Nature, 517(7535):455-9
Nat Commun, 6:7030
Matter H, Nuermberger E, Tyagi S,
Fraisse L, Grosset JH, Lagrange S,
9. Merker M, Blin C, Mona S, Duforet-
2. Boyle EC, Dombrowsky H, Sarau J,
Müller R (2015) Antibiotics. Targeting
Frebourg N, Lecher S, Willery E, Blum
Braun J, Aepfelbacher M, Lautenschläger I,
DnaN for tuberculosis therapy using novel MG, Rüsch-Gerdes S, Mokrousov I,
Grassl GA (2015) Ex vivo perfusion of the
griselimycins. Science, 348(6239):
Aleksic E, Allix-Béguec C, Antierens
isolated rat small intestine as a novel model
1106-12
A, Augustynowicz-Kopeć E, Ballif M,
of Salmonella enteritis. Am J Physiol
Barletta F, Beck HP, Barry CE 3rd,
Gastrointest Liver Physiol, 310(2):
6. Koutsoudakis G, Romero-Brey I,
Bonnet M, Borroni E, Campos-Herrero
G55-63
Berger C, Perez-Vilaro G, Monteiro Perin
I, Cirillo D, Cox H, Crowe S, Crudu V,
P, Vondran FW, Kalesse M, Harmrolfs
Diel R, Drobniewski F, Fauville-Dufaux
3. Hoffmann B, Tappe D, Höper D, Herden
K, Muller R, Martinez JP, Pietschmann
M, Gagneux S, Ghebremichael S,
C, Boldt A, Mawrin C, Niederstraßer O,
T, Bartenschlager R, Bronstrup M,
Hanekom M, Hoffner S, Jiao WW, Kalon
Müller T, Jenckel M, van der Grinten E,
Meyerhans A, Diez J (2015) Soraphen A:
S, Kohl TA, Kontsevaya I, Lillebæk T,
Lutter C, Abendroth B, Teifke JP, Cadar
A broad-spectrum antiviral natural product
Maeda S, Nikolayevskyy V, Rasmussen
D, Schmidt-Chanasit J, Ulrich RG, Beer
with potent anti-hepatitis C virus activity. M, Rastogi N, Samper S, Sanchez-Padilla
M (2015) A Variegated Squirrel Bornavirus
J Hepatol, 63(4):813-21
E, Savic B, Shamputa IC, Shen A, Sng
LH, Stakenas P, Toit K, Varaine F,
Associated with Fatal Human Encephalitis.
N Engl J Med, 373(2):154-62
7. Langhans B, Alwan AW, Kramer B,
Vukovic D, Wahl C, Warren R, Supply P,
Glassner A, Lutz P, Strassburg CP,
Niemann S, Wirth T (2015) Evolutionary
4. Keller L, Plaza A, Dubiella C, Groll M,
Nattermann J, Spengler U (2015) Regula-
history and global spread of the Mycobac-
Kaiser M, Müller R (2015) Macyranones:
tory CD4+ T cells modulate the interaction
terium tuberculosis Beijing lineage. Nat
Structure, Biosynthesis, and Binding Mode
between NK cells and hepatic stellate cells
Genet, 47(3):242-9
of an Unprecedented Epoxyketone that
by acting on either cell type. Targets the 20S Proteasome. J Am Chem
J Hepatol, 62(2):398-404
Soc, 137(25):8121-30
10. Pache L, Dutra MS, Spivak AM,
Marlett JM, Murry JP, Hwang Y, Maestre
8. Ling LL, Schneider T, Peoples AJ,
AM, Manganaro L, Vamos M, Teriete P,
5. Kling A, Lukat P, Almeida DV, Bauer
Spoering AL, Engels I, Conlon BP, Mueller
Martins LJ, König R, Simon V, Bosque A,
A, Fontaine E, Sordello S, Zaburannyi
A, Schäberle TF, Hughes DE, Epstein S,
Fernandez-Sesma A, Cosford ND,
* Impact factor in 2014
Bushman FD, Young JA, Planelles V,
15. Wolter F, Glassner A, Kramer B,
mice leads to pronounced induction of innate
Chanda SK (2015) BIRC2/cIAP1 Is a
Kokordelis P, Finnemann C, Kaczmarek
immune responses in comparison to HBV
Negative Regulator of HIV-1 Transcription
DJ, Goeser F, Lutz P, Nischalke HD,
mono-infection. J Hepatol 63(2):346-53
and Can Be Targeted by Smac Mimetics to
Strassburg CP, Spengler U, Nattermann J
Promote Reversal of Viral Latency. (2015) Hypoxia impairs anti-viral activity of
3. Haagmans BL, van den Brand JM,
Cell Host Microbe, 18(3):345-53
natural killer (NK) cells but has little effect on
Raj VS, Volz A, Wohlsein P, Smits SL,
anti-fibrotic NK cell functions in hepatitis C
Schipper D, Bestebroer TM, Okba N,
virus infection. J Hepatol, 63(6):1334-44
Fux R, Bensaid A, Solanes Foz D, Kuiken
T, Baumgärtner W, Segalés J, Sutter G,
K, Hassemer M, Finkernagel M, Carra
G, Nuebling M, Chudy M, Niekamp H,
16. Xia Y, Stadler D, Lucifora J, Reisinger
Osterhaus AD (2015) An orthopoxvirus-
Glebe D, Sarrazin C, Zeuzem S, Hildt E
F, Webb D, Hösel M, Michler T,
based vaccine reduces virus excretion after
(2015). Intracellular accumulation of sub-
Wisskirchen K, Cheng X, Zhang K, Chou
MERS-CoV infection in dromedary camels.
viral HBsAg particles and diminished Nrf2
WM, Wettengel JM, Malo A, Bohne F,
Science, 351(6268):77-81
activation in HBV genotype G expressing
Hoffmann D, Eyer F, Thimme R, Falk CS,
4. Vercauteren K, Brown RJ, Mesalam
cells lead to an increased ROI level.
Thasler WE, Heikenwalder M, Protzer U
AA, Doerrbecker J, Bhuju S, Geffers R,
J Hepatol, 62(4):791-8
(2015) Interferon-γ and Tumor Necrosis
Van Den Eede N, McClure CP, Troise
Factor-α Produced by T Cells Reduce
F, Verhoye L, Baumert T, Farhoudi A,
12. Stöhr S, Costa R, Sandmann L,
the HB Persistence Form, cccDNA,
Cortese R, Ball JK, Leroux-Roels G,
Westhaus S, Pfaender S, Anggakusuma,
Without Cytolysis. Gastroenterology,
Pietschmann T, Nicosia A, Meuleman P
Dazert E, Meuleman P, Vondran FW,
150(1):194-205
Manns MP, Steinmann E, von Hahn T,
(2015) Targeting a host-cell entry factor
barricades antiviral-resistant HCV variants
Ciesek S (2015) Host cell mTORC1 is
17. Yoh SM, Schneider M, Seifried J,
from on-therapy breakthrough in human-
required for HCV RNA replication Gut,
Soonthornvacharin S, Akleh RE, Olivieri
liver mice. Gut, 25. August 2015. doi:
14. August 2015. doi:10.1136/
KC, De Jesus PD, Ruan C, de Castro E,
10.1136/gutjnl-2014-309045 [Epub
gutjnl-2014-308971 [Epub ahead of
Ruiz PA, Germanaud D, des Portes V,
ahead of print]
print]
García-Sastre A, König R, Chanda SK
(2015) PQBP1 Is a Proximal Sensor of 13. Tripathi S, Pohl MO, Zhou Y,
the cGAS-Dependent Innate Response to
Rodriguez-Frandsen A, Wang G, Stein
HIV-1. Cell, 161(6):1293-305
53
Clinical Research
DA, Moulton HM, DeJesus P, Che J,
1. Agnandji ST, Huttner A, Zinser ME,
Mulder LC, Yángüez E, Andenmatten D,
Njuguna P, Dahlke C, Fernandes JF,
Pache L, Manicassamy B, Albrecht RA,
Preclinical Research
Gonzalez MG, Nguyen Q, Brass A, Elledge
Yerly S, Dayer JA, Kraehling V, Kasonta
R, Adegnika AA, Altfeld M, Auderset F,
S, White M, Shapira S, Hacohen N,
1. Dargel C, Bassani-Sternberg M,
Bache EB, Biedenkopf N, Borregaard S,
Karlas A, Meyer TF, Shales M, Gatorano
Hasreiter J, Zani F, Bockmann JH,
Brosnahan JS, Burrow R, Combescure
A, Johnson JR, Jang G, Johnson T,
Thiele F, Bohne F, Wisskirchen K, Wilde
C, Desmeules J, Eickmann M, Fehling SK,
Verschueren E, Sanders D, Krogan N,
S, Sprinzl MF, Schendel DJ, Krackhardt
Finckh A, Goncalves AR, Grobusch MP,
Shaw M, König R, Stertz S, García-Sastre
AM, Uckert W, Wohlleber D, Schiemann
Hooper J, Jambrecina A, Kabwende AL,
A, Chanda SK (2015) Meta- and Orthogonal
M, Stemmer K, Heikenwälder M, Busch
Kaya G, Kimani D, Lell B, Lemaitre B,
Integration of Influenza „OMICs“ Data
DH, Richter G, Mann M, Protzer U
Lohse AW, Massinga-Loembe M, Matthey
Defines a Role for UBR4 in Virus Budding.
(2015) T Cells Engineered to Express a
A, Mordmüller B, Nolting A, Ogwang
Cell Host Microbe, 18(6):723-35
T-Cell Receptor Specific for Glypican-3
C, Ramharter M, Schmidt-Chanasit J,
to Recognize and Kill Hepatoma Cells In
Schmiedel S, Silvera P, Stahl FR, Staines
14. Van ND, Falk CS, Sandmann L,
Vitro and in Mice. Gastroenterology,
HM, Strecker T, Stubbe HC, Tsofa B, Zaki
Vondran FW, Helfritz F, Wedemeyer H,
149(4):1042-52
S, Fast P, Moorthy V, Kaiser L, Krishna S,
Becker S, Kieny MP, Bejon P, Kremsner
Manns MP, Ciesek S, von Hahn T (2015)
PUBLICATIONS
11. Peiffer KH, Akhras S, Himmelsbach
Modulation of HCV reinfection after ortho-
2. Giersch K, Allweiss L, Volz T, Helbig M,
PG, Addo MM, Siegrist CA (2015) Phase
topic liver transplantation by fibroblast
Bierwolf J, Lohse AW, Pollok JM, Petersen
1 Trials of rVSV Ebola Vaccine in Africa
growth factor-2 and other non-interferon
J, Dandri M, Lütgehetmann M (2015)
and Europe – Preliminary Report. N Engl J
mediators. Gut, 65(6):1015-23
Hepatitis Delta co-infection in humanized
Med, 374(17):1647-60
DZIF ANNUAL REPORT 2015
2. Carroll MW, Matthews DA, Hiscox JA,
Gulick RM, Fätkenheuer G, Schlesinger
treatment of a patient in intensive care.
Elmore MJ, Pollakis G, Rambaut A, Hewson
SJ, Nussenzweig MC (2015) Viraemia
Lancet, 385(9976):1428-35
R, García-Dorival I, Bore JA, Koundouno
suppressed in HIV-1-infected humans by
R, Abdellati S, Afrough B, Aiyepada J,
broadly neutralizing antibody 3BNC117.
Akhilomen P, Asogun D, Atkinson B,
Nature, 522(7557):487-91
Badusche M, Bah A, Bate S, Baumann J,
Becker D, Becker-Ziaja B, Bocquin A,
4. Mader J, Gallo A, Schommartz T,
Borremans B, Bosworth A, Boettcher JP,
Handke W, Nagel CH, Günther P, Brune
Cannas A, Carletti F, Castilletti C, Clark
W, Reich K (2015) Calcium spirulan
S, Colavita F, Diederich S, Donatus A,
derived from Spirulina platensis inhibits
Duraffour S, Ehichioya D, Ellerbrok H,
herpes simple virus 1 attachment to
Fernandez-Garcia MD, Fizet A,
human keratinocytes and protects against
Fleischmann E, Gryseels S, Hermelink A,
herpes labialis. J Allergy Clin Immunol,
Hinzmann J, Hopf-Guevara U, Ighodalo
137(1):197-203
PUBLICATIONS
Y, Jameson L, Kelterbaum A, Kis Z, Kloth
54
S, Kohl C, Korva M, Kraus A, Kuisma E,
5. Maertens JA, Raad II, Marr KA,
Kurth A, Liedigk B, Logue CH, Lüdtke A,
Patterson TF, Kontoyiannis DP, Cornely
Maes P, McCowen J, Mély S, Mertens M,
OA, Bow EJ, Rahav G, Neofytos D, Aoun
Meschi S, Meyer B, Michel J, Molkenthin
M, Baddley JW, Giladi M, Heinz WJ,
P, Muñoz-Fontela C, Muth D, Newman
Herbrecht R, Hope W, Karthaus M, Lee
EN, Ngabo D, Oestereich L, Okosun J,
DG, Lortholary O, Morrison VA, Oren
Olokor T, Omiunu R, Omomoh E, Pallasch
I, Selleslag D, Shoham S, Thompson
E, Pályi B, Portmann J, Pottage T, Pratt C,
GR 3rd, Lee M, Maher RM, Schmitt-
Priesnitz S, Quartu S, Rappe J, Repits J,
Hoffmann AH, Zeiher B, Ullmann AJ
Richter M, Rudolf M, Sachse A, Schmidt
(2015) Isavuconazole versus voriconazole
KM, Schudt G, Strecker T, Thom R,
for primary treatment of invasive mould
Thomas S, Tobin E, Tolley H, Trautner J,
disease caused by Aspergillus and other
Vermoesen T, Vitoriano I, Wagner M,
filamentous fungi (SECURE): a phase 3,
Wolff S, Yue C, Capobianchi MR,
randomised-controlled, non-inferiority trial.
Kretschmer B, Hall Y, Kenny JG, Rickett
Lancet, 387(10020):760-9
NY, Dudas G, Coltart CE, Kerber R, Steer
D, Wright C, Senyah F, Keita S, Drury P,
6. Sagara I, Beavogui AH, Zongo I,
Diallo B, de Clerck H, Van Herp M,
Soulama I, Borghini-Fuhrer I, Fofana
Sprecher A, Traore A, Diakite M, Konde
B, Camara D, Somé AF, Coulibaly AS,
MK, Koivogui L, Magassouba N,
Traore OB, Dara N, Kabore MJ, Thera
Avšič-Županc T, Nitsche A, Strasser M,
I, Compaore YD, Sylla MM, Nikiema F,
Ippolito G, Becker S, Stoecker K, Gabriel
Diallo MS, Dicko A, Gil JP, Borrmann S,
M, Raoul H, Di Caro A, Wölfel R,
Duparc S, Miller RM, Doumbo OK, Shin
Formenty P, Günther S (2015) Temporal
J, Bjorkman A, Ouedraogo JB, Sirima SB,
and spatial analysis of the 2014-2015
Djimdé AA (2015) Safety and efficacy of
Ebola virus outbreak in West Africa.
re-treatments with pyronaridine-artesunate
Nature, 524(7563):97-101
in African patients with malaria: a substudy
3. Caskey M, Klein F, Lorenzi JC, Seaman
Infect Dis, 16(2):189-98
of the WANECAM randomised trial. Lancet
MS, West AP Jr, Buckley N, Kremer G,
Nogueira L, Braunschweig M, Scheid
7. Wolf T, Kann G, Becker S, Stephan C,
JF, Horwitz JA, Shimeliovich I, Ben-
Brodt HR, de Leuw P, Grünewald T, Vogl
Avraham S, Witmer-Pack M, Platten
T, Kempf VA, Keppler OT, Zacharowski
M, Lehmann C, Burke LA, Hawthorne
K (2015) Severe Ebola virus disease with
T, Gorelick RJ, Walker BD, Keler T,
vascular leakage and multiorgan failure:
Bernhard Nocht Institute for Tropical Medicine
Robert Koch Institute*
Bundeswehr Institute of Microbiology
Technische Universität Braunschweig
Federal Institute for Drugs and Medical Devices*
Technische Universität München
Friedrich-Loeffler-Institut*
TWINCORE–Centre for Experimental and
Clinical Infection Research
German Cancer Research Center
Giessen University
Hannover Medical School
Heidelberg University
Heidelberg University Hospital
Heinrich Pette Institute–Leibniz Institute for
Experimental Virology
Universität Hamburg
Universität zu Lübeck
University of Bonn
University of Cologne
University of Tübingen
University of Veterinary Medicine Hannover, Foundation
Helmholtz Centre for Infection Research
University Hospital Bonn
Helmholtz Zentrum München–German Research Center
for Environmental Health
University Hospital Cologne
Klinikum der Universität München
University Hospital Tübingen
University Medical Center Hamburg-Eppendorf
Klinikum rechts der Isar der Technischen
Universität München
Leibniz Institute DSMZ–German Collection of
Microorganisms and Cell Cultures
Ludwig-Maximilians-Universität München
Max Planck Institute for Developmental Biology
Mittelhessen University of Applied Sciences
Paul-Ehrlich-Institut
Philipps-Universität Marburg
Research Center Borstel–Leibniz-Center
for Medicine and Bioscience
MEMBER ESTABLISHMENTS
Member establishments of
the German Center for
Infection Research
* Member establishment since June 2015
55
DZIF ANNUAL REPORT 2015
Imprint
German Center for Infection Research (DZIF e.V.)
Main Office
Inhoffenstraße 7
D-38124 Braunschweig
T +49 (0)531-61 81-11 52
F +49 (0)531-61 81-11 53
[email protected]
www.dzif.de
IMPRINT
Project coordination: DZIF Press Office
Text: Dr Heidrun Riehl-Halen, Medizinkontext, and DZIF Press Office
English translation: Julia Kyambi
Photos: Title: HZI/Peer Lukat I p. 3/4: DZIF/Kurt Bauer I p.6: EmLab I p. 7 (top): NIAID I
p. 7 (bottom): DZIF/scienceRELATIONS I p. 8: Research Center Borstel I p. 9 (top): DZIF/
Christoph Lange I p. 9 (bottom): Research Center Borstel I p.10: Schwäbisches Tagblatt
Tübingen I p. 11 (top): BNITM/Ralf Krumkamp I p. 11 (bottom): DZIF/scienceRELATIONS I
p. 12: Michael Hölscher I p. 13 (top): MMRC/Sabi I p. 13 (bottom): DZIF/scienceRELATIONS I
p. 14: DZIF/scienceRELATIONS I p. 15 (top): TWINCORE/Pietschmann, Gentzsch I p. 15
(bottom): DZIF/scienceRELATIONS I p. 16: HZI/Manfred Rohde I p. 17 (top): HZI/F. Bierstedt
56
I p. 17 (bottom): DZIF/scienceRELATIONS I p. 18: Helmholtz Zentrum München I p. 19 (top)
Helmholtz Zentrum München I p. 19 (bottom): DZIF/scienceRELATIONS I p. 20: JLU Press office/
Katrina Friese I p. 21 (top): IMMIH, Köln/Axel Hamprecht I p. 21 (bottom): Evelina Tacconelli I
p. 22: Achim Hörauf I p. 23 (top): HZI/Peer Lukat I p. 23 (bottom): DZIF/scienceRELATIONS I
p. 24 (top): DZIF/scienceRELATIONS I p. 24 (bottom): Paul-Ehrlich-Institut I p. 25: Medizin
FotoKöln I p. 26 (top): Uni Tübingen/Peter Kremsner I p. 26 (bottom): Bernhard Nocht Institute
I p. 27 (top: HIPS/Bellhäuser I p. 27 (bottom): Helmholtz Institute for Pharmaceutical Research
Saarland/Saarland University I p. 28: Heidelberg University Hospital I p. 29 (top): Andreas
Bremges I p. 29 (bottom): Helmholtz Centre for Infection Research I p. 30 (top): TU München I
p. 30 (bottom): DZIF/scienceRELATIONS I p. 31: Daelin/Fotolia.com I p. 32 (top): drawing:
Sophia Halamoda I p. 32 (bottom): cdc/F.A. Murphy I p. 33 (top left): Michael Hölscher I p. 33
(top centre): Research Center Borstel I p. 33 (right centre): MHH I p. 34: DZIF/Kurt Bauer I
p. 35 (top): Factum I p. 35 (bottom): DZIF/Sascha Gramann I p. 36: DZIF/Kurt Bauer I p. 39: DLR
Projektträger/BMBF
Funded by:
Bayerisches Staatsministerium für
Bildung und Kultus, Wissenschaft und Kunst
German Center for Infection Research (DZIF e.V.)
Main Office
Inhoffenstraße 7
D-38124 Braunschweig
T +49 (0)531-61 81-11 52
F +49 (0)531-61 81-11 53
[email protected]
www.dzif.de
© August 2016