Descripción del proyecto
Desarrollo de vacunas en caso de variación antigénica
La vacunación es la forma más eficaz de prevenir enfermedades infecciosas. Sin embargo, no existen vacunas para patógenos que presentan variaciones antigénicas elevadas como la gripe y los virus VIH-1. Para combatir eficazmente la infección de estos patógenos, la respuesta inmunitaria debe producir anticuerpos específicos para epítopos conservados no variables con el fin de proteger contra la mayoría de cepas. El equipo del proyecto VIVA, financiado con fondos europeos, se propone desarrollar vacunas para que la respuesta inmunitaria acabe produciendo anticuerpos ampliamente neutralizantes contra la infección del virus VIH-1. Los investigadores estudiarán la regulación de la maduración de la afinidad de las células B en un sistema inmunitario policlonal como respuesta a antígenos complejos. Si los resultados del proyecto son satisfactorios, se podrá generar un nuevo tipo de vacunas que pueda producir respuestas inmunitarias contra patógenos con variaciones antigénicas, incluidas posibles enfermedades de nueva aparición.
Objetivo
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.
Ámbito científico
- 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
Palabras clave
Programa(s)
Régimen de financiación
ERC-STG - Starting GrantInstitución de acogida
17177 Stockholm
Suecia