tetano
Editor, Senior Moderator
Sci Transl Med
. 2025 Jan;17(779):eadr8373.
doi: 10.1126/scitranslmed.adr8373. Epub 2025 Jan 1. Vaccination with different group 2 influenza subtypes alters epitope targeting and breadth of hemagglutinin stem-specific human B cells
Grace E Mantus[SUP] 1 [/SUP], Ankita J Chopde[SUP] 1 [/SUP], Jason Gorman[SUP] 1 2 [/SUP], Lauren Y Cominsky[SUP] 1 [/SUP], Amine Ourahmane[SUP] 1 [/SUP], Adrian Creanga[SUP] 1 [/SUP], Geoffrey D Shimberg[SUP] 1 [/SUP], Rebecca A Gillespie[SUP] 1 [/SUP], David J Van Wazer[SUP] 1 [/SUP], Tongqing Zhou[SUP] 1 [/SUP], Suprabhath R Gajjala[SUP] 1 [/SUP], Connor Williams[SUP] 3 [/SUP], Emma Maestle[SUP] 3 [/SUP], Douglas S Reed[SUP] 3 [/SUP], Leonid Serebryannyy[SUP] 1 [/SUP], Pamela Costner[SUP] 1 [/SUP], Lasonji Holman[SUP] 1 [/SUP], Joseph P Casazza[SUP] 1 [/SUP], Richard A Koup[SUP] 1 [/SUP], Lesia K Dropulic[SUP] 1 [/SUP], Peter D Kwong[SUP] 1 [/SUP], Adrian B McDermott[SUP] 1 [/SUP], Masaru Kanekiyo[SUP] 1 [/SUP], Sarah F Andrews[SUP] 1 [/SUP]
Affiliations
The conserved influenza hemagglutinin stem, which is a target of cross-neutralizing antibodies, is now used in vaccine strategies focused on protecting against influenza pandemics. Antibody responses to group 1 stem have been extensively characterized, but little is known about group 2. Here, we characterized the stem-specific repertoire of individuals vaccinated with one of three group 2 influenza subtypes (H3, H7, or H10). Epitope mapping revealed two epitope supersites on the group 2 stem. Antibodies targeting the central epitope were broadly cross-reactive, whereas antibodies targeting the lower epitope had narrower breadth but higher potency against H3 subtypes. The ratio of B cells targeting each of the supersites varied with the vaccine subtype, leading to differences in the cross-reactivity of the B cell response. Our findings suggest that vaccine strategies targeting both group 2 stem epitopes would be complementary, eliciting broader and more potent protection against both seasonal and pandemic influenza strains.
. 2025 Jan;17(779):eadr8373.
doi: 10.1126/scitranslmed.adr8373. Epub 2025 Jan 1. Vaccination with different group 2 influenza subtypes alters epitope targeting and breadth of hemagglutinin stem-specific human B cells
Grace E Mantus[SUP] 1 [/SUP], Ankita J Chopde[SUP] 1 [/SUP], Jason Gorman[SUP] 1 2 [/SUP], Lauren Y Cominsky[SUP] 1 [/SUP], Amine Ourahmane[SUP] 1 [/SUP], Adrian Creanga[SUP] 1 [/SUP], Geoffrey D Shimberg[SUP] 1 [/SUP], Rebecca A Gillespie[SUP] 1 [/SUP], David J Van Wazer[SUP] 1 [/SUP], Tongqing Zhou[SUP] 1 [/SUP], Suprabhath R Gajjala[SUP] 1 [/SUP], Connor Williams[SUP] 3 [/SUP], Emma Maestle[SUP] 3 [/SUP], Douglas S Reed[SUP] 3 [/SUP], Leonid Serebryannyy[SUP] 1 [/SUP], Pamela Costner[SUP] 1 [/SUP], Lasonji Holman[SUP] 1 [/SUP], Joseph P Casazza[SUP] 1 [/SUP], Richard A Koup[SUP] 1 [/SUP], Lesia K Dropulic[SUP] 1 [/SUP], Peter D Kwong[SUP] 1 [/SUP], Adrian B McDermott[SUP] 1 [/SUP], Masaru Kanekiyo[SUP] 1 [/SUP], Sarah F Andrews[SUP] 1 [/SUP]
Affiliations
- PMID: 39742506
- DOI: 10.1126/scitranslmed.adr8373
The conserved influenza hemagglutinin stem, which is a target of cross-neutralizing antibodies, is now used in vaccine strategies focused on protecting against influenza pandemics. Antibody responses to group 1 stem have been extensively characterized, but little is known about group 2. Here, we characterized the stem-specific repertoire of individuals vaccinated with one of three group 2 influenza subtypes (H3, H7, or H10). Epitope mapping revealed two epitope supersites on the group 2 stem. Antibodies targeting the central epitope were broadly cross-reactive, whereas antibodies targeting the lower epitope had narrower breadth but higher potency against H3 subtypes. The ratio of B cells targeting each of the supersites varied with the vaccine subtype, leading to differences in the cross-reactivity of the B cell response. Our findings suggest that vaccine strategies targeting both group 2 stem epitopes would be complementary, eliciting broader and more potent protection against both seasonal and pandemic influenza strains.