National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
75N93021C00015
United States
Citation
Journal: Cell Host Microbe / Year: 2026 Title: Childhood immunological imprinting of cross-subtype antibodies targeting the hemagglutinin head domain of influenza viruses. Authors: Shuk Hang Li / Bo Wang / Gyunghee Jo / Artem Mikelov / Reilly K Atkinson / Valerie Le Sage / Colleen Furey / Jordan T Ort / Naiqing Ye / Sydney Gang / Ruhi Shah / Jefferson J S Santos / ...Authors: Shuk Hang Li / Bo Wang / Gyunghee Jo / Artem Mikelov / Reilly K Atkinson / Valerie Le Sage / Colleen Furey / Jordan T Ort / Naiqing Ye / Sydney Gang / Ruhi Shah / Jefferson J S Santos / Katharina Röltgen / Shilpa A Joshi / Ji-Yeun Lee / Taylor A Pursell / Elizabeth M Drapeau / Julianna Han / Amy P Callear / Ronald G Collman / Arnold S Monto / Emily T Martin / Seema S Lakdawala / Andrew B Ward / Ian A Wilson / Scott D Boyd / Scott E Hensley / Abstract: Influenza virus cross-subtype antibodies targeting epitopes in the hemagglutinin (HA) head are rare because these epitopes are variable between influenza virus subtypes. We found that a large ...Influenza virus cross-subtype antibodies targeting epitopes in the hemagglutinin (HA) head are rare because these epitopes are variable between influenza virus subtypes. We found that a large proportion of monoclonal antibodies (mAbs) isolated from individuals immunized with the 2021-22 seasonal influenza vaccine bound to an epitope on the HA head of both the H1N1 vaccine strain and H3N2 strains from the mid-1990s. The unmutated common ancestors of many of these mAbs reacted to both the 1990s H3s and the 2021-22 H1 vaccine strain. These cross-subtype antibodies were also found in polyclonal sera, but only among individuals born in the 1990s. Ferrets sequentially exposed to a 1990s H3N2 virus and contemporary influenza vaccine also produced H1/H3 cross-reactive antibodies. Recently, H1N1 viruses have acquired a substitution that abrogates the binding of these antibodies. Together, our study demonstrates how prior influenza virus exposures can influence the specificity of antibodies elicited by entirely different influenza virus subtypes.
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