EMD-42532

Single-particle
2.7 Å
EMD-42532 Deposition: 30/10/2023
Map released: 08/05/2024
Last modified: 13/11/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-42532

CryoEM structure of A/Perth/16/2009 H3 in complex with polyclonal Fab from mice immunized with H3 stem nanoparticles-28 days post immunization

EMD-42532

Single-particle
2.7 Å
EMD-42532 Deposition: 30/10/2023
Map released: 08/05/2024
Last modified: 13/11/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Mus musculus, Influenza A virus
Sample: A/Perth/16/2009 H3
Fitted models: 8ut7 (Avg. Q-score: 0.591)

Deposition Authors: Huang J, Han J, Ward AB
Eliciting a single amino acid change by vaccination generates antibody protection against group 1 and group 2 influenza A viruses.
PUBMED: 38670113
DOI: doi:10.1016/j.immuni.2024.03.022
ISSN: 1074-7613
ASTM: IUNIEH
Abstract:
Broadly neutralizing antibodies (bnAbs) targeting the hemagglutinin (HA) stem of influenza A viruses (IAVs) tend to be effective against either group 1 or group 2 viral diversity. In rarer cases, intergroup protective bnAbs can be generated by human antibody paratopes that accommodate the conserved glycan differences between the group 1 and group 2 stems. We applied germline-engaging nanoparticle immunogens to elicit a class of cross-group bnAbs from physiological precursor frequency within a humanized mouse model. Cross-group protection depended on the presence of the human bnAb precursors within the B cell repertoire, and the vaccine-expanded antibodies enriched for an N55T substitution in the CDRH2 loop, a hallmark of the bnAb class. Structurally, this single mutation introduced a flexible fulcrum to accommodate glycosylation differences and could alone enable cross-group protection. Thus, broad IAV immunity can be expanded from the germline repertoire via minimal antigenic input and an exceptionally simple antibody development pathway.