tetano
Editor, Senior Moderator
Nat Med
. 2022 Feb 3.
doi: 10.1038/s41591-021-01636-8. Online ahead of print.
A single residue in influenza virus H2 hemagglutinin enhances the breadth of the B cell response elicited by H2 vaccination
Sarah F Andrews[SUP] 1 [/SUP], Julie E Raab[SUP] #[/SUP][SUP] 2 [/SUP], Jason Gorman[SUP] #[/SUP][SUP] 2 [/SUP], Rebecca A Gillespie[SUP] #[/SUP][SUP] 2 [/SUP], Crystal S F Cheung[SUP] #[/SUP][SUP] 2 [/SUP], Reda Rawi[SUP] #[/SUP][SUP] 2 [/SUP], Lauren Y Cominsky[SUP] 2 [/SUP], Jeffrey C Boyington[SUP] 2 [/SUP], Adrian Creanga[SUP] 2 [/SUP], Chen-Hsiang Shen[SUP] 2 [/SUP], Darcy R Harris[SUP] 2 [/SUP], Adam S Olia[SUP] 2 [/SUP], Alexandra F Nazzari[SUP] 2 [/SUP], Tongqing Zhou, Katherine V Houser[SUP] 2 [/SUP], Grace L Chen[SUP] 2 [/SUP], John R Mascola[SUP] 2 [/SUP], Barney S Graham[SUP] 2 [/SUP], Masaru Kanekiyo[SUP] 2 [/SUP], Julie E Ledgerwood[SUP] 2 [/SUP], Peter D Kwong[SUP] 2 [/SUP], Adrian B McDermott[SUP] 3 [/SUP]
Affiliations
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[SUB]HA2[/SUB] predicted to sterically clash with HA stem-binding antibodies characterized to date. To understand the effect of Phe45[SUB]HA2[/SUB], 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.
. 2022 Feb 3.
doi: 10.1038/s41591-021-01636-8. Online ahead of print.
A single residue in influenza virus H2 hemagglutinin enhances the breadth of the B cell response elicited by H2 vaccination
Sarah F Andrews[SUP] 1 [/SUP], Julie E Raab[SUP] #[/SUP][SUP] 2 [/SUP], Jason Gorman[SUP] #[/SUP][SUP] 2 [/SUP], Rebecca A Gillespie[SUP] #[/SUP][SUP] 2 [/SUP], Crystal S F Cheung[SUP] #[/SUP][SUP] 2 [/SUP], Reda Rawi[SUP] #[/SUP][SUP] 2 [/SUP], Lauren Y Cominsky[SUP] 2 [/SUP], Jeffrey C Boyington[SUP] 2 [/SUP], Adrian Creanga[SUP] 2 [/SUP], Chen-Hsiang Shen[SUP] 2 [/SUP], Darcy R Harris[SUP] 2 [/SUP], Adam S Olia[SUP] 2 [/SUP], Alexandra F Nazzari[SUP] 2 [/SUP], Tongqing Zhou, Katherine V Houser[SUP] 2 [/SUP], Grace L Chen[SUP] 2 [/SUP], John R Mascola[SUP] 2 [/SUP], Barney S Graham[SUP] 2 [/SUP], Masaru Kanekiyo[SUP] 2 [/SUP], Julie E Ledgerwood[SUP] 2 [/SUP], Peter D Kwong[SUP] 2 [/SUP], Adrian B McDermott[SUP] 3 [/SUP]
Affiliations
- PMID: 35115707
- DOI: 10.1038/s41591-021-01636-8
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[SUB]HA2[/SUB] predicted to sterically clash with HA stem-binding antibodies characterized to date. To understand the effect of Phe45[SUB]HA2[/SUB], 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.