Mechanisms that promote the evolution of cross-reactive antibodies upon vaccination with designed influenza immunogens.
Cell Rep
; 42(3): 112160, 2023 03 28.
Article
em En
| MEDLINE
| ID: mdl-36867533
ABSTRACT
Immunogens that elicit broadly neutralizing antibodies targeting the conserved receptor-binding site (RBS) on influenza hemagglutinin may serve as candidates for a universal influenza vaccine. Here, we develop a computational model to interrogate antibody evolution by affinity maturation after immunization with two types of immunogens a heterotrimeric "chimera" hemagglutinin that is enriched for the RBS epitope relative to other B cell epitopes and a cocktail composed of three non-epitope-enriched homotrimers of the monomers that comprise the chimera. Experiments in mice find that the chimera outperforms the cocktail for eliciting RBS-directed antibodies. We show that this result follows from an interplay between how B cells engage these antigens and interact with diverse helper T cells and requires T cell-mediated selection of germinal center B cells to be a stringent constraint. Our results shed light on antibody evolution and highlight how immunogen design and T cells modulate vaccination outcomes.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Vacinas contra Influenza
/
Influenza Humana
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article