Description du projet
Un vaccin pionnier contre la diarrhée pourrait réussir là où ses prédécesseurs échouaient
La diarrhée est généralement une nuisance non menaçante dans les civilisations occidentales, mais elle est mortelle dans les pays en développement, en particulier chez les enfants de moins de cinq ans. Dans les cas où les enfants survivent, la malnutrition liée à la pauvreté est aggravée par la déshydratation et la sous-nutrition sévère résultant de l’infection. Cela peut avoir des effets à long terme sur le développement physique et cognitif. SHIGETECVAX développe un nouveau vaccin oral contre deux bactéries étroitement liées qui sont les principales causes de la diarrhée. Basé sur des antigènes non ciblés dans les vaccins précédents, il est beaucoup plus sûr, permettant des doses plus élevées. Potentiellement plus efficace contre les deux agents pathogènes, ce vaccin pourrait sauver des millions de vies.
Objectif
Although vaccination is an effective way to reduce the huge disease burden associated with diarrhoea caused by enteric pathogens, many attempts to develop vaccines for shigellosis and ETEC infections have failed and a number of current approaches are too complex and costly to provide an adequate solution for LMICs. This Consortium is dedicated to advancing a radically new approach against Shigella and ETEC based not on the immunodominant, but highly variable Shigella LPS O-antigen, target of almost all past and current vaccine development efforts. There are four pillars on which the ShigETEC vaccine has been designed: (i) Elimination of the LPS O-antigen to allow recognition of multiple antigens on the cell surface that are shared among different serotypes of Shigella and are increasingly being recognized as important in protection from shigellosis. These antigens are also closely related to those of ETEC and may also help in protecting against that pathogen as well. (ii) Elimination of the invasiveness of Shigella by disruption of the invasion complex resulting in a much safer/less reactogenic oral vaccine that can take advantage of gut mucosal immunity, possibly allowing administration of high vaccine doses and therefore addresses the low immunogenicity seen with other live attenuated vaccine candidates. (iii) Addition of detoxified toxin antigens of ETEC that will induce neutralizing/blocking antibodies to these critical virulence factors. (iv) Rational molecular design of ShigETEC will allow future generations of vaccines to include additional antigens for other pathogens. The work programme entails manufacture of clinical trial material, first-in-human testing for safety and immunogenicity in non-endemic adults, a sero-epidemiology study to learn about natural immune response to the vaccine, and importantly testing the vaccine in endemic populations. The Consortium comprises partners from EU and Bangladesh that bring along highly complementary expertise.
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RIA - Research and Innovation actionCoordinateur
69115 Heidelberg
Allemagne