Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Feb;28(2):373-382.
doi: 10.1038/s41591-021-01636-8. Epub 2022 Feb 3.

A single residue in influenza virus H2 hemagglutinin enhances the breadth of the B cell response elicited by H2 vaccination

Sarah F Andrews  1 , Julie E Raab #  2 , Jason Gorman #  2 , Rebecca A Gillespie #  2 , Crystal S F Cheung #  2 , Reda Rawi #  2 , Lauren Y Cominsky  2 , Jeffrey C Boyington  2 , Adrian Creanga  2 , Chen-Hsiang Shen  2 , Darcy R Harris  2 , Adam S Olia  2 , Alexandra F Nazzari  2 , Tongqing Zhou, Katherine V Houser  2 , Grace L Chen  2 , John R Mascola  2 , Barney S Graham  2 , Masaru Kanekiyo  2 , Julie E Ledgerwood  2 , Peter D Kwong  2 , Adrian B McDermott  3
Affiliations

A single residue in influenza virus H2 hemagglutinin enhances the breadth of the B cell response elicited by H2 vaccination

Sarah F Andrews et al. Nat Med. 2022 Feb.

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.

PubMed Disclaimer

References

    1. Iuliano, A. D. et al. Estimates of global seasonal influenza-associated respiratory mortality: a modelling study. Lancet 391, 1285–1300 (2018). - PubMed - DOI
    1. Ellebedy, A. H. et al. Induction of broadly cross-reactive antibody responses to the influenza HA stem region following H5N1 vaccination in humans. Proc. Natl Acad. Sci. USA 111, 13133–13138 (2014). - PubMed - PMC - DOI
    1. Li, G. M. et al. Pandemic H1N1 influenza vaccine induces a recall response in humans that favors broadly cross-reactive memory B cells. Proc. Natl Acad. Sci. USA 109, 9047–9052 (2012). - PubMed - PMC - DOI
    1. Wrammert, J. et al. Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection. J. Exp. Med. 208, 181–193 (2011). - PubMed - PMC - DOI
    1. Andrews, S. F. et al. Immune history profoundly affects broadly protective B cell responses to influenza. Sci. Transl. Med. 7, 316ra192 (2015). - PubMed - PMC - DOI

Publication types

Associated data