Description du projet
Le développement d’un vaccin en cas de variation antigénique
La vaccination est la solution la plus efficace pour prévenir les maladies infectieuses. Toutefois, aucun vaccin n’est développé pour les agents pathogènes subissant de fortes variations antigéniques comme le virus de la grippe et le VIH-1. Afin de lutter efficacement contre l’infection dans le cas de ces agents pathogènes, la réponse immunitaire doit se traduire par des anticorps spécifiques pour des épitopes conservés non variables destinés à protéger contre la majorité des souches. Le projet VIVA, financé par l’UE, entend développer des vaccins pour obtenir une réponse immunitaire menant à la production d’anticorps neutralisants à large spectre contre l’infection au VIH-1. Les chercheurs étudieront la régulation de la maturation par affinité des cellules B dans un système immunitaire polyclonal en réponse à des antigènes complexes. La réussite du projet permettrait de générer une nouvelle classe de vaccins qui peuvent entraîner des réponses immunitaires efficaces contre des agents pathogènes subissant des variations antigéniques, y compris contre de potentielles maladies émergentes.
Objectif
Vaccination is the most effective strategy to prevent infectious diseases but despite years of research there are no vaccines against variable pathogens such as HIV-1. Contrary to what is required for non-variable pathogens, vaccines against genetically variable pathogens need to elicit antibodies specific for conserved epitopes to protect against the majority of strains. These antibodies are termed broadly neutralizing antibodies (bNAbs). bNAbs against the genetically variable HIV-1 surface protein Env are highly somatically mutated and develop in a fraction of infected individuals, but have thus far failed to be elicited by vaccination. For a vaccine to elicit antibodies against a specific epitope of a variable pathogen, it needs to specifically expand rare precursor cells in the presence of a polyclonal B cell response that bind other parts of the same antigen. Furthermore, it needs to guide the rare precursor cells through repeated germinal center reactions to induce high numbers of somatic mutations, a critical characteristic for the potency of HIV-1 bNAbs. To develop such vaccines, we need to understand the regulation of antigen-driven affinity maturation of B cells in a polyclonal immune system in response to complex antigens. To study this, we will perform immunization experiments of wild type mice, adoptively transferred to include a limited pool of naïve B cells from novel HIV-1 Env-specific human antibody knock-in mice. In contrast to conventional antibody knock-in mice that have been used to study B cell activation previously, naïve precursor B cells from these knock-in mice are specific for a complex pathogen-derived antigen. Detailed characterization of the immune responses that develop in response to Env- and non-Env-based antigens, will enable us to generate vaccines that more efficiently drive protective immune responses against variable pathogens such as HIV-1 and Influenza, as well as potential emerging diseases.
Champ scientifique
- medical and health sciencesbasic medicineimmunologyimmunisation
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- medical and health scienceshealth sciencesinfectious diseasesRNA virusesinfluenza
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsvaccines
- natural sciencesbiological sciencesgeneticsmutation
Programme(s)
Thème(s)
Régime de financement
ERC-STG - Starting GrantInstitution d’accueil
17177 Stockholm
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