tetano
Editor, Senior Moderator
Cell Rep
. 2023 Mar 1;42(3):112160.
doi: 10.1016/j.celrep.2023.112160. Online ahead of print.
Mechanisms that promote the evolution of cross-reactive antibodies upon vaccination with designed influenza immunogens
Leerang Yang[SUP] 1 [/SUP], Timothy M Caradonna[SUP] 2 [/SUP], Aaron G Schmidt[SUP] 3 [/SUP], Arup K Chakraborty[SUP] 4 [/SUP]
Affiliations
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.
Keywords: CP: Immunology; affinity maturation; antigen capture; antigen valency; helper T cell; immune focusing; immunogen design; in silico; mechanism; selection.
. 2023 Mar 1;42(3):112160.
doi: 10.1016/j.celrep.2023.112160. Online ahead of print.
Mechanisms that promote the evolution of cross-reactive antibodies upon vaccination with designed influenza immunogens
Leerang Yang[SUP] 1 [/SUP], Timothy M Caradonna[SUP] 2 [/SUP], Aaron G Schmidt[SUP] 3 [/SUP], Arup K Chakraborty[SUP] 4 [/SUP]
Affiliations
- PMID: 36867533
- DOI: 10.1016/j.celrep.2023.112160
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.
Keywords: CP: Immunology; affinity maturation; antigen capture; antigen valency; helper T cell; immune focusing; immunogen design; in silico; mechanism; selection.