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Team 4: Immunity to vaccines -


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Head: Behazine Combadiere

Immunity to vaccines

Despite the impact of world-wide vaccination programs, which have significantly reduced the incidence of infectious diseases and mortality, there is still a great need to develop new generations of vaccines, safer that induce long-lasting immunity and can be effectively administered by simple, economical, practical and reproducible immunization procedures. Promising approaches for innovation include modifications of the mode of vaccine applications (e.g. transcutaneous, mucosal), better targeting of high numbers of antigen-presenting cells (APC) and mechanism improving APC activation (adjuvants) and vaccine compounds-uptake (particle-based vaccines).

Induction of T cell responses has become a major goal in therapeutic vaccination against viral diseases and cancers. We propose to ameliorate T cell immunity by facilitating by targeting the vaccine compounds into skin resident antigen-presenting cells. We have previously shown in a human clinical trial that transcutaneous vaccination can lead to major CD8 cellular responses compared to conventional IM route, which is more efficient for humoral responses. Indeed, differential targeting of epidermal or dermal antigen-presenting cells could lead to differential quality of immune responses. We develop two principal axes: 1) humanized-murine models engrafted with human skin and peripheral lymphoid cell precursors in order to study the impact of vaccine penetration by transcutaneous (TC) or intradermal (ID) routes on the induction of immune responses using various vaccine candidates (DNA, bio-degradable nanoparticles, MVA) and to study the mechanism of immune responses, 2) clinical trials comparing routes of vaccination and studying the quality of immune responses to vaccines (i.e. inactivated influenza vaccine, vaccinia virus…). In the face of the complexity of immunological events related to infectious diseases, it can be expected that only combinations of multiple new approaches will succeed in the development of new vaccination strategies that can lead to the control of infectious diseases.

The team is taking part in the european project CUTHIVAC http://www.cuthivac.eu/Nouvelle fenêtre