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TitleVaccination with different group 2 influenza subtypes alters epitope targeting and breadth of hemagglutinin stem-specific human B cells.
Journal, issue, pagesSci Transl Med, Vol. 17, Issue 779, Page eadr8373, Year 2025
Publish dateJan 1, 2025
AuthorsGrace E Mantus / Ankita J Chopde / Jason Gorman / Lauren Y Cominsky / Amine Ourahmane / Adrian Creanga / Geoffrey D Shimberg / Rebecca A Gillespie / David J Van Wazer / Tongqing Zhou / Suprabhath R Gajjala / Connor Williams / Emma Maestle / Douglas S Reed / Leonid Serebryannyy / Pamela Costner / Lasonji Holman / Joseph P Casazza / Richard A Koup / Lesia K Dropulic / Peter D Kwong / Adrian B McDermott / Masaru Kanekiyo / Sarah F Andrews /
PubMed AbstractThe 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 ...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.
External linksSci Transl Med / PubMed:39742506
MethodsEM (single particle)
Resolution3.65 - 3.96 Å
Structure data

44901

9bu6

EMDB-44901, PDB-9bu6:
Vaccine elicited Fab C968.180 with influenza H10 JD13 HA trimer
Method: EM (single particle) / Resolution: 3.65 Å

44903

9bu8

EMDB-44903, PDB-9bu8:
Vaccine elicited Fab c115.131 with influenza H10 JD13 HA trimer
Method: EM (single particle) / Resolution: 3.96 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • influenza a virus
  • homo sapiens (human)
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / Vaccine / VIRAL PROTEIN-IMMUNE SYSTEM complex / IMMUNE SYSTEM

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