8UWA

VH1-18 QxxV class antibody 09-1B12 bound to A/Perth/16/2009 H3N2 hemagglutinin

Summary for 8UWA

• Entry DOI: 10.2210/pdb8uwa/pdb
• Descriptor: 09-1B12 light chain, alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-3)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (11 entities in total)
• Functional Keywords: antibody, stem, influenza, hemagglutinin, viral protein-immune system complex, viral protein/immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 9
• Total formula weight: 338428.06

Authors

Maurer, D.P. (deposition date: 2023-11-06, release date: 2024-05-08, Last modification date: 2024-10-16)

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

X-RAY DIFFRACTION (4.02 Å)