Mechanisms that promote the evolution of cross-reactive antibodies upon vaccination with designed influenza immunogens
Name
1-s2.0-S2211124723001717-main.pdf
Description
Published version
Size
4.72 MB
Format
Adobe PDF
Checksum (MD5)
6324ec9f55e07c9d24367af0c7cdd24e
Author(s)
Yang, Leerang
Caradonna, Timothy M
Schmidt, Aaron G
Chakraborty, Arup K
Date Issued
March 2023
Journal
Cell Reports
Publisher
Elsevier BV
Citation
Yang, Leerang, Caradonna, Timothy M, Schmidt, Aaron G and Chakraborty, Arup K. 2023. "Mechanisms that promote the evolution of cross-reactive antibodies upon vaccination with designed influenza immunogens." Cell Reports, 42 (3).
Version
Final published version
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.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
Ragon Institute of MGH, MIT and Harvard
Massachusetts Institute of Technology. Department of Physics
Massachusetts Institute of Technology. Department of Chemistry
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/j.celrep.2023.112160
