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Title | A single residue in influenza virus H2 hemagglutinin enhances the breadth of the B cell response elicited by H2 vaccination. |
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Journal, issue, pages | Nat Med, Vol. 28, Issue 2, Page 373-382, Year 2022 |
Publish date | Feb 3, 2022 |
Authors | Sarah F Andrews / Julie E Raab / Jason Gorman / Rebecca A Gillespie / Crystal S F Cheung / Reda Rawi / Lauren Y Cominsky / Jeffrey C Boyington / Adrian Creanga / Chen-Hsiang Shen / Darcy R Harris / Adam S Olia / Alexandra F Nazzari / Tongqing Zhou / Katherine V Houser / Grace L Chen / John R Mascola / Barney S Graham / Masaru Kanekiyo / Julie E Ledgerwood / Peter D Kwong / Adrian B McDermott / |
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- ...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. |
External links | Nat Med / PubMed:35115707 |
Methods | EM (single particle) |
Resolution | 2.85 - 3.87 Å |
Structure data | EMDB-23098, PDB-7l0l: EMDB-23816, PDB-7mfg: |
Chemicals | ChemComp-NAG: |
Source |
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Keywords | IMMUNE SYSTEM/Viral protein / VRC / IMMUNE SYSTEM / VRC316 / H2 / Fab / Flu / IMMUNE SYSTEM-Viral protein complex / VIRAL PROTEIN/IMMUNE SYSTEM / VRC310 / H1 / VIRAL PROTEIN-IMMUNE SYSTEM complex |