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Aditec workpackages
Work package 1: Vaccine Adjuvants
Objectives:
The main objective of this WP is to perform comparative evaluation of existing ADITEC adjuvants for
selected prototype antigens and to develop 2nd generation adjuvants with improved potency and
safety.
Work package 2: Vaccine vectors
Objectives: The general objective of WP2 is the pre-clinical development of vaccine vectors for
optimized induction of protective polyvalent immune responses.
Work package 3: Formulations and delivery devices
Objectives:
The primary objective of WP3 is to facilitate the introduction of new vaccine/adjuvant candidates
optimized for ”alternate” (non-IM/parenteral) routes of administration, including relevant formulations
and specific delivery devices (where relevant), and to assure that vaccine candidates can be tested
and compared across platforms. The aim of this WP is to work within the consortium to ensure that
multiple routes of administration are available on an “as needed” basis, that each vaccine candidate is
assured to be formulated in an optimal way depending on the device used, and that all the relevant
analytics are available to make valid cross-route comparisons.
Workpackage 4: Routes of Immunization
Objectives:
Development of alternative routes of immunization is urgently needed for prevention of mucosal
respiratory, enteric and genital infections as well as a means for making overall vaccine administration
safer and simpler.The anatomical location, magnitude and quality of the immune response induced by
mucosal immunization are determined by the immunization route, the adjuvant and the formulation
and/or delivery system used and remain largely poorly studied. The objectives of this WP are to clarify
these relationships as studied in mice using well-defined antigens and adjuvants:
1. Compare mucosal and systemic immune responses and immunologic memory induced by different
routes of immunization, with special emphasis on comparing the potential and limitations of recently
described sublingual, aerosol and dermal/transdermal immunization routes with previously tested
mucosal and systemic routes.
2. Validate, refine and standardize current tools and develop new tools for assessment of mucosal
immunity in pre-clinical studies.
3. Define anatomic localization, magnitude and quality of immune responses induced by different
vaccine antigen-adjuvant formulations, vectors and devices as derived and/or provided from the work
in WP 1-3 .
4. Characterise priming and trafficking of T and B cells following immunization by different routes of
immunization. These studies will use vaccine antigens that allow comparisons of the same molecule
tested as “subunit” antigen and as a component of bacterial or viral vectors and ideally selected to also
allow testing of induced protection against challenge in mouse models. These antigens will include
those (influenza, TB) selected to be used across the whole ADITEC program and selected antigens
will be tested with selected adjuvants as defined in WP1 and in the formulations, vectors and delivery
devices provided by the work in WP1-3. A special study will compare the mucosal and systemic
immune responses to two commercially available mucosal vaccines, cold-adapted influenza vaccine
FluMist™ and B-subunit/whole cell cholera vaccine Dukoral™ , when administered by sublingual
versus the approved nasal and oral routes, respectively. The studies will also pave the way for and be
a link to more downstream ADITEC studies/WPs: prime-boost studies (WP5); protection and other
studies in advanced animal models (WP6); and pivotal clinical studies ( WP10-13).
Work package 5: Prime-boost Strategies
Objectives:
The overall objectives of the present WP are to identify optimal prime-boost vaccination strategies, by
using different vaccine formulations and combination of mucosal/systemic immunization routes
developed in WP1-4 and to characterise primary immune responses and their correlation with immune
memory responses (in collaboration with WP10-13).
Specific objectives will be:
1. Identification of optimal heterologous prime-boost vaccination strategies that combine different
vaccine formulations and mucosal/systemic immunization routes.
2. Characterise priming and trafficking of T cells following immunization using different vaccine
formulations.
3. Establish in vivo and ex vivo pre-clinical models to study the T-cell priming properties of adjuvants
and delivery systems.
4. Characterize T cell priming by vaccination in humans and its relevance in predicting secondary
responses.
Work package 6: Advanced Animal Models
Objectives:
To use advanced challenge models with human pathogens (TB and Influenza) to discover new
mechanisms associated with vaccine induced protective response and select of vaccine candidates to
be advanced to the clinic.
Work package 7: Aging and early life
Objectives:
The general objective of this WP is to analyze the effects of new vaccine formulations in animal
models at extreme of age and to collect clinical evidences on age-associated determinants of
response to currently licensed vaccines. Neonates, infants and elderly persons will be focused on. The
final goals will be to collect data on candidate vaccines which should be considered for use at the
extremes of age and to improve the scientific evidence on which to base recommendations defining
how these particular age groups should be vaccinated to achieve optimal protection.
Work package 8: Molecular signatures of immunity and immunogenicity
Objectives:
WP8 will assess the human immune response to vaccination and infection at the level of the
transcriptomic and proteomic response, T-cell and B-cell memory formation, cell trafficking, and key
molecular pathways of innate immunity, with emphasis on underlying mechanisms of protective
immunity. In particular, we will investigate the following questions, outlined in the specific objectives:
1. To establish an extended multiplex transcriptome profiling assay (RT-MLPA) for monitoring
(longitudinal) differences in expression of innate and adaptive immune-response and signaling genes,
in order to interrogate, evaluate and optimize novel immunization strategies (LUMC).
2. To compare global transcriptomic gene expression profiles (mRNA as well as micro-RNA) following
vaccination (e.g. with a new live vaccine (rec. BCG)) in infants and adults; we will thus identify novel
mechanisms and correlates of immunity and safety with particular emphasis on age (MPG).
3. To determine quantitative profiles of proteins selected from transcriptomics data following
vaccination. We will combine these results with data from the above transcriptomic analysis to identify
novel signatures and mechanisms of immunity (Novartis, MPG, LUMC).
4. To identify key mechanisms of inducing memory T-cell (including Th17) and B-cell responses
involved in mucosal immunity and protection, and to determine the underlying BCR and TCR
repertoires and key molecules orchestrating mucosal migration (IRB).
5. To design strategies to prevent immune suppression and cellular exhaustion, and stimulate optimal
vaccine-induced memory and effector functions to interfere with chronic persisting infection (MPG)
6. To evaluate key molecular markers of innate immunity, and its regulation in mucosal immunity and
protection in human and animal models (FHR).
7. To test stress inducing agents as enhancers of innate and memory immune responses (KCL).
Work package 9: Systems biology of innate and adaptive immunity to adjuvanted influenza
vaccination in humans
Objectives:
The aim of WP9 will be to perform a systems biological analysis of the innate and adaptive immune
responses to vaccination of humans. The main focus will be on studies with the influenza vaccines,
either with or without adjuvants, conducted in WP10 and WP7. The systems biology approach will be
also possibly applied to other vaccines, such as meningococcal vaccines and other studies conducted
in WP10-13. The overarching goal of this effort is to identify molecular signatures that correlate with,
and predict, various key parameters of the innate and adaptive immune response. A secondary goal is
to obtain insights into the molecular mechanisms driving innate and adaptive responses to vaccination.
Work package 10: Profiling human responses to defined adjuvants and prime-boost strategies
Objectives:
1.To characterise biomics of human responses to defined adjuvant technologies
2.To characterise human cellular and humoral responses after heterologous prime-boost
3.To study breadth of human T cell responses induced by different adjuvants
Work package 11: Evaluation in humans of novel routes of immunisation to induce targeted
and disseminated immunity
Objectives:
1. To define generic methodologies to induce broad human immunity at diverse anatomical sites by
anatomically targeted immunisation
2. To evaluate human immune responses to sublingual antigen delivery
Work package 12: Human transcriptomic and immune responses to enteric bacterial challenge
& prophylactic immunisation
Objectives:
1. Characterise human transcriptomic and immune responses to enteric bacterial challenge infection &
prophylactic immunisation
2. Correlate transcriptomic and immune responses with protection against infection and shedding of
bacteria
Work package 13: Phase 1 clinical trials of novel immunisation technologies
Objectives:
To evaluate novel immunisation technologies in Phase 1 clinical trials.
Work package 14: Effects of human genetics, gender and disease
Objectives:
There is a large individual variation in vaccine responses and most vaccines do not elicit protective
immunity in all vaccines. The aim of WP14 will be to assess the effects on genetic variation, gender
and disease on vaccine responses. Specific objectives will be:
1. To assess the effect of gender and underlying disease on vaccine response, in particular
autoimmune and chronic inflammatory diseases, like cardiovascular disease.
2. To discover novel sequence variants (single polymorphic nucleotides, SNPs) that contribute vaccine
response, using as models lack of/low and high response to influenza vaccination (performed in the
project) or lack of response or adverse events to smallpox vaccination (existing data).
3. To to assess the association of such ”vaccine response SNPs” with autoimmune and inflammatory
diseases, and to validate their effects on response to other vaccines and effects of adjuvants and
immunization strategies tested in the patient characterization studies and clinical trials (WP10-13).
Work package 15: Regulatory and ethical issues
Objectives:
1. To identify regulatory challenges to novel technologies for immunisation and develop enabling
regulatory frameworks
2. To identify challenges to standardisation of novel technologies for immunisation and develop
enabling regulatory frameworks
Work package 16: Training
Objectives:
A set of internationally recognized training programs at three levels will be developed with the specific
aim to foster and disseminate throughout Europe specialised knowledge in the field of translational
immunology and vaccinology, to improve and disseminate these advanced research skills developed
within the project, and to promote the mobility and exchanges between students and SMEs
researchers of the participating institutions.
Work package 17: Dissemination
Objectives:
1. Dissemination
2. Visibility
Work package 18: Management
Objectives:
• Scientific and administrative coordination of the project
• To guarantee the successful progress of the project within the agreed time, cost and quality limits as
defined by the project contract signed with the EU and the Consortium Agreement signed among the
participants.
• To establish effective communication among the consortium partners.
• To identify, protect and manage the Intellectual Property (IP) generated by the project and patent
applications.
Work package 19: Enhancing Impact – vaccine research and innovation
Objectives:
• Commissioned vaccine/immunology research for SMEs
• Venture funds and loans for SMEs
• Detecting and securing exploitable IP
• Commissioned vaccine/immunology research for public health
• Dissemination, visibility, advocacy
• Impact monitoring: Impact Score Card
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