Helmholtz Centre for Infection Research (HZI)

http://www.helmholtz-hzi.de/en/

Carlos.Guzman@helmholtz-hzi.de

The Helmholtz Centre for Infection Research (HZI) is a member of the Helmholtz Association, the largest scientific organization in Germany bringing together 18 scientific-technical and biological-medical research centres. The mission of the HZI, with its main campus in Braunschweig, is to rise to the societal challenges of infectious diseases by investigating their fundamental mechanisms of pathogenesis. For this, research focuses on three main topics: “Bacterial and viral pathogens”, “Immune response and immune interventions” and “Anti-infectives”. The key questions that the scientists at the HZI address are: How do bacteria and viruses make us sick? How does the immune system fight these pathogens? And which substances can protect us from infections in the future? The ultimate aim is to derive innovative approaches for the prevention, diagnosis and therapy of infectious diseases. To ensure the most effective translation of basic research results to application, the HZI also intensively collaborates with clinical partners. The centre employs around 900 employees from various professional sectors, originating from over 40 countries, and has an annual budget of over 50 million euros (2016).

Role in the TRANSVAC project

The HZI will provide expertise and technologies for adjuvants and the preclinical validation of vaccine technologies and candidates in murine systems. The HZI will develop a vaccination protocol for mucosal administration based on three novel strategies: (i) development and optimization of a vaccination protocol in which parenterally-primed T and B cells are subsequently pulled into the mucosa by the local delivery of the cognate antigen to the requested effector site, (ii) testing the co-administration of antigens with novel mucosal adjuvants using different mucosal immunisation routes and schedules, and (iii) testing various nanoparticles co-administered with different immunomodulators for their ability to generate both systemic and mucosal immune responses following transcutaneous/trans-follicular vaccination. Selected mucosal vaccine candidates as well as additional novel adjuvant formulations will be tested for immunogenicity in mice. Furthermore, the mode of action of different adjuvant and antigen formulations will be studied, with the overall aim to develop adjuvant formulations ready for pre-clinical and ultimately clinical development. The HZI will also not only perform experiments to compare the predictive immunogenicity and efficacy of vaccines between different model species and humans but will test comparative effects of adjuvants. Finally, the HZI will help develop in vivo imaging technologies to characterize (i) vaccine biodistribution and persistence, and (ii) cellular and molecular changes at the injection site and in draining lymphoid tissues, helping to refine the use of animal models.

Main staff involved in TRANSVAC

Prof. Carlos A. Guzmán, MD. PhD; Dr. Thomas Ebensen; Dr. Kai Schulze; Dr. Peggy Riese; Dr. Blair Prochnow;

The Facility

The scientific work at the HZI Department of Vaccinology and Applied Microbiology includes the elucidation of mechanisms of host responses to infection and vaccination, discovering new mucosal adjuvants, and developing and validating vaccines against specific infectious diseases. For this, conventional and advanced murine models are ideally suited to perform a cost-efficient screening, selection and prioritization of vaccine candidates. The department features expertise, technology and infrastructure in the fields of adjuvants, immune modulators and formulation, including mucosal adjuvants. Our experts in mucosal vaccine delivery have established in vitro and in vivo models to assess the activity of adjuvants and vaccine formulations on innate and adaptive immune cells, as well their capacity to stimulate different effector mechanisms of clearance. The team has access to state-of-the-art laboratories and animal facilities with BSL2 and BSL3 containment, flow cytometry, cell sorting, histopathology and in vivo imaging (IVIS).

TNA or Training provided

The HZI will provide access to its formulation and characterization services for candidate antigens paired with mucosal adjuvants. The service will include formulation, stability testing and the physicochemical characterization of adjuvants and vaccines, including advanced immune system monitoring. This service will allow users to improve the compatibility and stability of their vaccine antigen with different mucosal adjuvants (from the HZI portfolio) and to define the optimal production methods to generate immunogenic vaccine candidates with optimised physicochemical stability (in vitro studies). A summary of the results obtained with each formulation will be provided. Material suitable for preclinical in vivo immunisation studies will be provided to the customer. The HZI will also provide access to laboratory and animal facilities up to BSL3 and conventional, modified (e.g. knockout, knock-in, reporter) and humanised (e.g. immune system) mice as animal models. We will evaluate the immunogenicity of vaccine candidates (provided by user) administered by systemic, transdermal or mucosal routes and will monitor humoral responses and cellular responses. We offer challenge studies with conventional and humanized mice including animal health and pathogen monitoring. We also offer passive cell transfer studies, generation of bone marrow chimeras, in vivo imaging (IVIS), determination of the microbiome, and histopathology.

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