7L0L

Cryo-EM structure of the VRC316 clinical trial, vaccine-elicited, human antibody 316-310-1B11 in complex with an H2 CAN05 HA trimer

Summary for 7L0L

• Entry DOI: 10.2210/pdb7l0l/pdb
• EMDB information: 23098
• Descriptor: 316-310-1B11 Light Chain, Hemagglutinin HA1 chain, Hemagglutinin HA2 chain, ... (5 entities in total)
• Functional Keywords: vrc, immune system, vrc316, h2, fab, flu, immune system-viral protein complex, immune system/viral protein
• Biological source: Homo sapiens; More
• Total number of polymer chains: 12
• Total formula weight: 341768.00

Authors

Gorman, J.,Kwong, P.D. (deposition date: 2020-12-11, release date: 2021-11-03, Last modification date: 2022-03-09)

Primary citation

Andrews, S.F.,Raab, J.E.,Gorman, J.,Gillespie, R.A.,Cheung, C.S.F.,Rawi, R.,Cominsky, L.Y.,Boyington, J.C.,Creanga, A.,Shen, C.H.,Harris, D.R.,Olia, A.S.,Nazzari, A.F.,Zhou, T.,Houser, K.V.,Chen, G.L.,Mascola, J.R.,Graham, B.S.,Kanekiyo, M.,Ledgerwood, J.E.,Kwong, P.D.,McDermott, A.B.
A single residue in influenza virus H2 hemagglutinin enhances the breadth of the B cell response elicited by H2 vaccination.
Nat Med, 28:373-382, 2022

PubMed Abstract: Conserved epitopes on the influenza hemagglutinin (HA) stem are an attractive target for universal vaccine strategies as they elicit broadly neutralizing antibodies. Such antibody responses to stem-specific epitopes have been extensively characterized for HA subtypes H1 and H5 in humans. H2N2 influenza virus circulated 50 years ago and represents a pandemic threat due to the lack of widespread immunity, but, unlike H1 and H5, the H2 HA stem contains Phe45 predicted to sterically clash with HA stem-binding antibodies characterized to date. To understand the effect of Phe45, we compared the HA stem-specific B cell response in post hoc analyses of two phase 1 clinical trials, one testing vaccination with an H2 ferritin nanoparticle immunogen ( NCT03186781 ) and one with an inactivated H5N1 vaccine ( NCT01086657 ). In H2-naive individuals, the magnitude of the B cell response was equivalent, but H2-elicited HA stem-binding B cells displayed greater cross-reactivity than those elicited by H5. However, in individuals with childhood H2 exposure, H5-elicited HA stem-binding B cells also displayed high cross-reactivity, suggesting recall of memory B cells formed 50 years ago. Overall, we propose that a one-residue difference on an HA immunogen can alter establishment and expansion of broadly neutralizing memory B cells. These data have implications for stem-based universal influenza vaccination strategies.

PubMed: 35115707
DOI: 10.1038/s41591-021-01636-8

Experimental method

ELECTRON MICROSCOPY (2.85 Å)