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 Phe45HA2 predicted to sterically clash with HA stem-binding antibodies characterized to date. To understand the effect of Phe45HA2, 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.
|
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 |
Journal | Nature medicine
(Nat Med)
Vol. 28
Issue 2
Pg. 373-382
(02 2022)
ISSN: 1546-170X [Electronic] United States |
PMID | 35115707
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
|
Copyright | © 2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply. |
Chemical References |
- Antibodies, Neutralizing
- Antibodies, Viral
- Epitopes
- Hemagglutinin Glycoproteins, Influenza Virus
- Hemagglutinins
- Influenza Vaccines
|
Topics |
- Antibodies, Neutralizing
- Antibodies, Viral
- Child
- Clinical Trials, Phase I as Topic
- Epitopes
- Hemagglutinin Glycoproteins, Influenza Virus
- Hemagglutinins
- Humans
- Influenza A Virus, H5N1 Subtype
- Influenza Vaccines
- Influenza, Human
- Vaccination
|