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BROADimmune

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Structural genetic and functional analyses of broadly neutralizing antibodies a...

Structural genetic and functional analyses of broadly neutralizing antibodies against human pathogens The overall goal of this project is to understand the molecular mechanisms that lead to the generation of potent and broadly neutralizing antibodies against medically relevant pathogens, and to identify the factors that limit thei... ver más

30/09/2020

IRB

2M€

Presupuesto del proyecto: 2M€

Líder del proyecto

FONDAZIONE PER LISTITUTO DI RICERCA IN BIOMED... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

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Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2020-09-30

ERC-ADG-2014: ERC Advanced Grant Scope:Objectives

I+D

Cerrada hace 10 años

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Características del participante

Este proyecto no cuenta con búsquedas de partenariado abiertas en este momento.

Información adicional privada

No hay información privada compartida para este proyecto. Habla con el coordinador.

2 Participantes

IRB

1.87M€ | Lider

ULMA SERVICIOS DE MANUTENCIO...

239.15K€ | Participante

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Duración del proyecto: 60 meses Fecha Inicio: 2015-09-30
Fecha Fin: 2020-09-30

Líder del proyecto

FONDAZIONE PER LISTITUTO DI RICERCA IN BIOMED... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 2M€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto The overall goal of this project is to understand the molecular mechanisms that lead to the generation of potent and broadly neutralizing antibodies against medically relevant pathogens, and to identify the factors that limit their production in response to infection or vaccination with current vaccines. We will use high-throughput cellular screens to isolate from immune donors clonally related antibodies to different sites of influenza hemagglutinin, which will be fully characterized and sequenced in order to reconstruct their developmental pathways. Using this approach, we will ask fundamental questions with regards to the role of somatic mutations in affinity maturation and intraclonal diversification, which in some cases may lead to the generation of autoantibodies. We will combine crystallography and long time-scale molecular dynamics simulation to understand how mutations can increase affinity and broaden antibody specificity. By mapping the B and T cell response to all sites and conformations of influenza hemagglutinin, we will uncover the factors, such as insufficient T cell help or the instability of the pre-fusion hemagglutinin, that may limit the generation of broadly neutralizing antibodies. We will also perform a broad analysis of the antibody response to erythrocytes infected by P. falciparum to identify conserved epitopes on the parasite and to unravel the role of an enigmatic V gene that appears to be involved in response to blood-stage parasites. The hypotheses tested are strongly supported by preliminary observations from our own laboratory. While these studies will contribute to our understanding of B cell biology, the results obtained will also have translational implications for the development of potent and broad-spectrum antibodies, for the definition of correlates of protection, and for improving vaccine design.

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