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TitleChildhood immunological imprinting of cross-subtype antibodies targeting the hemagglutinin head domain of influenza viruses.
Journal, issue, pagesCell Host Microbe, Vol. 34, Issue 5, Page 873-887.e11, Year 2026
Publish dateMay 13, 2026
AuthorsShuk 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 /
PubMed AbstractInfluenza 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.
External linksCell Host Microbe / PubMed:42049037
MethodsEM (single particle) / X-ray diffraction
Resolution2.15 - 20.0 Å
Structure data

EMDB-72527: Negative stain map of A/California/07/2009 H1N1 HA in complex with 97_F7 IgG
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-72528: Negative stain map of A/California/07/2009 H1N1 HA in complex with 88_B4 IgG
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-72529: Negative stain map of A/California/07/2009 H1N1 HA in complex with 3_H2 IgG
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-72530: Negative stain map of A/California/07/2009 H1N1 HA in complex with 49_C09 IgG
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-72531: Negative stain map of A/California/07/2009 H1N1 HA in complex with 33_C08 IgG
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-72532: Negative stain map of A/California/07/2009 H1N1 HA in complex with 33_C02 IgG
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-72533: Negative stain map of A/California/07/2009 H1N1 HA in complex with 18_D11 IgG
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-72534: Negative stain map of A/New York/631/1996 H3N2 HA in complex with 97_F7 IgG
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-72535: Negative stain map of A/New York/631/1996 H3N2 HA in complex with 88_B4 IgG
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-72536: Negative stain map of A/New York/631/1996 H3N2 HA in complex with 33_C08 IgG
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-72537: Negative stain map of A/New York/631/1996 H3N2 HA in complex with 18_D11 IgG
Method: EM (single particle) / Resolution: 20.0 Å

PDB-9y3x:
Crystal structure of hemagglutinin from H1N1 Influenza A virus A/California/04/2009 bound to the 3_H2 antibody
Method: X-RAY DIFFRACTION / Resolution: 3.39 Å

PDB-9y3y:
Crystal structure of hemagglutinin from H1N1 Influenza A virus A/California/04/2009 bound to the 49_C09 antibody
Method: X-RAY DIFFRACTION / Resolution: 3.8 Å

PDB-9y3z:
Crystal structure of hemagglutinin head domain from H3N2 Influenza A virus A/New York/631/1996 bound to the 3_H2 antibody
Method: X-RAY DIFFRACTION / Resolution: 2.15 Å

PDB-9y40:
Crystal structure of hemagglutinin head domain from H3N2 Influenza A virus A/New York/631/1996 bound to the 49_C09 antibody
Method: X-RAY DIFFRACTION / Resolution: 3.71 Å

PDB-9y41:
Crystal structure of hemagglutinin head domain from H1N1 Influenza A virus A/Victoria/2570/2019 bound to the 49_C09 antibody
Method: X-RAY DIFFRACTION / Resolution: 2.89 Å

Chemicals

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

ChemComp-PO4:
PHOSPHATE ION

ChemComp-HOH:
WATER

Source
  • homo sapiens (human)
  • influenza a virus (a/california/04/2009(h1n1))
  • influenza a virus (a/new york/631/1996(h3n2))
  • influenza a virus
KeywordsANTIVIRAL PROTEIN / Hemagglutinin / Head antibody / Influenza / Complex

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