Descrizione del progetto
Sviluppo di un vaccino in caso di variazione antigenica
La vaccinazione è il modo più efficace per prevenire le malattie infettive. Tuttavia, non esistono vaccini sviluppati per agenti patogeni con elevate variazioni antigeniche quali i virus dell’influenza e dell’HIV-1. Per combattere efficacemente l’infezione nel caso di tali agenti patogeni, la risposta immunitaria deve provocare anticorpi specifici per epitopi conservati non variabili per proteggere dalla maggior parte dei ceppi. Il progetto VIVA, finanziato dall’UE, si propone di sviluppare vaccini per la risposta immunitaria che portino alla produzione di anticorpi ampiamente neutralizzanti contro l’infezione da virus HIV-1. I ricercatori studieranno la regolazione della maturazione dell’affinità delle cellule B in un sistema immunitario policlonale in risposta ad antigeni complessi. I risultati positivi del progetto consentirebbero la generazione di una nuova classe di vaccini in grado di stimolare risposte immunitarie efficaci contro i patogeni con variazioni antigeniche, comprese le potenziali malattie emergenti.
Obiettivo
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.
Campo scientifico
- 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
Programma(i)
Argomento(i)
Meccanismo di finanziamento
ERC-STG - Starting GrantIstituzione ospitante
17177 Stockholm
Svezia