8UT6

CryoEM structure of A/Perth/16/2009 H3 in complex with polyclonal Fab from mice immunized with H3 stem nanoparticles-15 days post immunization

Summary for 8UT6

• Entry DOI: 10.2210/pdb8ut6/pdb
• EMDB information: 42531
• Descriptor: H3D15 pFab HC Fv_polyA, H3D15 pFab LC Fv_polyA, Hemagglutinin, ... (5 entities in total)
• Functional Keywords: cryoempem, flu hemagglutinin, central stem epitope, vh1-18, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Influenza A virus; More
• Total number of polymer chains: 5
• Total formula weight: 213223.64

Authors

Huang, J.,Han, J.,Ward, A.B. (deposition date: 2023-10-30, release date: 2024-05-08, Last modification date: 2024-11-06)

Primary citation

Ray, R.,Nait Mohamed, F.A.,Maurer, D.P.,Huang, J.,Alpay, B.A.,Ronsard, L.,Xie, Z.,Han, J.,Fernandez-Quintero, M.,Phan, Q.A.,Ursin, R.L.,Vu, M.,Kirsch, K.H.,Prum, T.,Rosado, V.C.,Bracamonte-Moreno, T.,Okonkwo, V.,Bals, J.,McCarthy, C.,Nair, U.,Kanekiyo, M.,Ward, A.B.,Schmidt, A.G.,Batista, F.D.,Lingwood, D.
Eliciting a single amino acid change by vaccination generates antibody protection against group 1 and group 2 influenza A viruses.
Immunity, 57:1141-1159.e11, 2024

PubMed 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.

PubMed: 38670113
DOI: 10.1016/j.immuni.2024.03.022

Experimental method

ELECTRON MICROSCOPY (2.8 Å)