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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 1 , Ankita J Chopde 1 , Jason Gorman 1 2 , Lauren Y Cominsky 1 , Amine Ourahmane 1 , Adrian Creanga 1 , Geoffrey D Shimberg 1 , Rebecca A Gillespie 1 , David J Van Wazer 1 , Tongqing Zhou 1 , Suprabhath R Gajjala 1 , Connor Williams 3 , Emma Maestle 3 , Douglas S Reed 3 , Leonid Serebryannyy 1 , Pamela Costner 1 , Lasonji Holman 1 , Joseph P Casazza 1 , Richard A Koup 1 , Lesia K Dropulic 1 , Peter D Kwong 1 , Adrian B McDermott 1 , Masaru Kanekiyo 1 , Sarah F Andrews 1
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 1 , Ankita J Chopde 1 , Jason Gorman 1 2 , Lauren Y Cominsky 1 , Amine Ourahmane 1 , Adrian Creanga 1 , Geoffrey D Shimberg 1 , Rebecca A Gillespie 1 , David J Van Wazer 1 , Tongqing Zhou 1 , Suprabhath R Gajjala 1 , Connor Williams 3 , Emma Maestle 3 , Douglas S Reed 3 , Leonid Serebryannyy 1 , Pamela Costner 1 , Lasonji Holman 1 , Joseph P Casazza 1 , Richard A Koup 1 , Lesia K Dropulic 1 , Peter D Kwong 1 , Adrian B McDermott 1 , Masaru Kanekiyo 1 , Sarah F Andrews 1
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.