Download International team led by Humabs BioMed identifies novel

International team led by Humabs BioMed identifies novel therapeutic antibody
candidates isolated from Zika-infected patients.
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Broad implications for new strategies to develop Zika virus diagnostics and treatments
Data published in Science*
Bellinzona, Switzerland, July 14, 2016 – Humabs BioMed SA, a Swiss antibody therapeutics
company, today announced a publication in the renowned scientific journal Science describing
an in-depth analysis of the human antibody and T cell immune response to the Zika virus
infection with implications for diagnostics, vaccine and treatment development.* The article is
the result of an international team led by Humabs.
Zika virus is a mosquito-borne flavivirus with homology to Dengue virus. After its introduction
into Brazil in 2015, Zika virus has spread rapidly in Latin America and in February 2016, the
World Health Organization (WHO) declared it a Public Health Emergency of International
Concern. While the main route of Zika virus infection is through bites by mosquitos, the virus
may also be spread sexually and vertically from mother to child during pregnancy. Most of the
Zika virus infections are asymptomatic or cause only mild symptoms. However, Zika virus
infection can lead to neurological complications, such as Guillain-Barré Syndrome in adults
and, of even greater concern, congenital birth defects such as microcephaly and other defects
in the developing fetus. As of today, there is no preventive vaccine or specific therapy
available.
The study published in Science reports the first characterization of the human immune
response to ZIKV infection, showing that most of the antibodies elicited by Zika virus infection
cross-react with Dengue virus. These cross-reactive antibodies are poorly neutralizing, but can
potently enhance Zika virus and Dengue virus infection in vitro. Antibody-dependent
enhancement occurs through binding of the tail of antibodies to Fc receptors that are found on
multiple cell types, including macrophages and placental endothelial cells. These receptors
can internalize viral particles coated by antibodies leading to virus replication and spread in
cells otherwise not targeted by the virus. Since placental Fc receptors transfer maternal
antibodies to the developing fetus, maternal antibodies to Dengue virus may also possibly help
Zika virus transmission across the placenta. The antibody-dependent enhancement
phenomenon is well known in cases of secondary Dengue infections, representing a risk factor
for the development of a more severe disease. Importantly, the study demonstrates that crossreactive antibodies induced by Zika virus infection can lethally enhance infection by Dengue
virus, suggesting that Zika virus infection in humans may predispose to more severe infections
with Dengue virus. “In contrast to the broad cross-reactivity observed with antibodies, we
found that the T cell responses is to a large extent Zika-specific, a finding that may mitigate the
severity of Dengue infection in Zika immune individuals,” said Federica Sallusto, co-last author
of the study and Director of the Center of Medical Immunology at the IRB.
The study also illustrates the use of antibodies specific for the Zika virus in a blockade-ofbinding assay that might be used as a highly specific serological diagnostic tool in large cohort
clinical and epidemiological studies to investigate the risk of Zika virus disease enhancement
and the real incidence rate of Zika virus congenital infection in areas endemic for other
flaviviruses.
In the diagram, from the top left, the Zika virus infection that can occur by mosquito; in the centre the
human immune response to infection, and to the right the isolation of the specific Zika antibody and
relative target virus. Below, the “super antibody” LALA that curbs the infection, either by mosquitohuman infection (to the left) or towards the foetus (to the right).
A highly potent neutralizing antibody was identified and engineered into the “LALA” form to not
bind Fc receptors and shown to inhibit the enhancement of Zika virus infection by plasma
derived from either Zika virus or Dengue virus infected patients and to protect animals when
given before and after animals were challenged lethally with Zika virus. This class of highly
potent antibodies holds the promise of being developed in their LALA versions as therapeutics
to both prevent congenital Zika virus infection in pregnant women at risk of contracting Zika
virus infection by directly neutralizing Zika virus, and also to serve as potential inhibitors of
disease enhancement and transplacental infection by pre-existing cross-reactive antibodies.
Image of the LALA antibody: in red the part bound to the virus,
in grey the “tail” of the antibody (named Fc) that binds the
receptors of the antibodies present on the different types of
cells, and in yellow the LALA mutation that blocks the binding
of the antibody to the receptors.
“It took only four months to functionally select, clone and characterize more than 100 anti-Zika
virus antibodies from the initial screening of human B cells derived from four convalescent
patients. The most potent antibody capable to neutralize Zika virus in a preclinical model is
now being developed by Humabs as an effective anti-Zika virus therapy to prevent congenital
infections. I believe that our discoveries will also have a significant impact on the development
of novel diagnostic approaches,” said Davide Corti, CSO of Humabs.
“This study represents another example of the rapid pathway established at Humabs for the
isolation of large numbers of anti-infective antibodies and for the discovery and development
of the best in class antibodies as potential new therapies against emerging pathogens,” said
Filippo Riva, CEO of Humabs.
The study is the result of an international collaboration between the Swiss Biotech company
Humabs BioMed SA and the Institute for Research in Biomedicine (IRB), Università della
Svizzera italiana (USI), together with the University of California, Berkeley (US), Public Health
England, Porton Down (UK), the Policlinico San Matteo IRCCS, Pavia (IT), the Swiss Tropical
and Public Health Institute, Basel (CH), and the Centre for Tropical Medicine, Ho Chi Minh City
(VN). The study was partially funded by the Swiss National Science Foundation and the
European Research Council, the US National Institutes of Health and the Italian Ministry of
Health.
* "Specificity, cross-reactivity and function of antibodies elicited by Zika virus infection," by K. Stettler;
M. Beltramello; S. Bianchi; F. Vanzetta; A. Minola; S. Jaconi; E. Cameroni; D. Corti at Humabs BioMed
SA in Bellinzona, Switzerland; D.A. Espinosa; E. Harris at University of California, Berkeley in Berkeley,
CA; V. Graham; S. Dowall; B. Atkinson; R. Hewson at Public Health England in Salisbury, UK; A.
Cassotta; F. Mele; M. Foglierini; M. Pedotti; L. Simonelli; L. Varani; A. Lanzavecchia; F. Sallusto at
Università della Svizzera italiana in Bellinzona, Switzerland; A. Cassotta; A. Lanzavecchia at ETH
Zurich in Zurich, Switzerland; E. Percivalle; F. Baldanti at Fondazione IRCCS Policlinico San Matteo in
Pavia, Italy; C.P. Simmons at University of Oxford in Oxford, UK; C.P. Simmons at Center for Tropical
Medicine in Ho Chi Minh City, Vietnam; C.P. Simmons at University of Melbourne in Melbourne, VIC,
Australia; C.P. Simmons at Peter Doherty Institute in Melbourne, VIC, Australia; J. Blum at Swiss
Tropical and Public Health Institute in Basel, Switzerland; J. Blum at University of Basel in Basel,
Switzerland. http://science.sciencemag.org/lookup/doi/10.1126/science.aaf8505
About Humabs BioMed SA
Humabs BioMed is a leading Swiss antibody therapeutics company that rapidly discovers and
develops superior antibodies directly derived from individuals who have successfully overcome
major diseases. These "winner antibodies" have already passed natural selection by the
immune system in response to disease and can easily be developed for standardized
therapeutic use. The company currently focuses on infectious diseases, but also has selected
antibodies against inflammatory diseases in the pipeline.
Humabs BioMed has established a unique technology platform and know-how allowing the
selection of monoclonal antibodies from immortalized human memory B cells and plasma
cells. To date, the company has closed four major licensing deals with top pharmaceutical
companies generating significant revenues. Two of these programs, partnered with
MedImmune and Novartis, respectively, are currently in clinical development.
Humabs BioMed Inquiries
Humabs BioMed SA
Dr. Davide Corti, CSO
Tel.: +41 91 825 63 80
E-mail: [email protected]
Media Inquiries
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Ines-Regina Buth / Dr. Ludger Weß, Managing Partners
Tel.: +49 30 23632768 or
+49 40 88165964
E-mail: [email protected]