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VIVA

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Vaccine development against variable pathogens

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, vacci... ver más

31/01/2025

2M€

Presupuesto del proyecto: 2M€

Líder del proyecto

KAROLINSKA INSTITUTET No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Ver 2 Participantes

Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2019-10-29

ERC-2019-STG: ERC Starting Grant

I+D

Cerrada hace 6 años

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2 Participantes

1.75M€ | Lider

Teknia Elorrio, S.L

899.94K€ | Participante

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Duración del proyecto: 63 meses Fecha Inicio: 2019-10-29
Fecha Fin: 2025-01-31

Líder del proyecto

KAROLINSKA INSTITUTET No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 2M€

Descripción del proyecto 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.

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