Genetically restricted human antibodies recognize a conserved β-hairpin in postfusion influenza hemagglutinin

Germline-encoded IGHV1-2 residues are required for human antibodies to recognize a conserved β-hairpin in postfusion influenza hemagglutinin, and 75% of people have the needed alleles.

• Why it matters: Genetic restriction limits how reliably “public” broadly protective antibodies can be generated, even when they target a conserved influenza epitope across many subtypes.
• What they did: The study used in vitro immunoassays and high-resolution cryogenic electron microscopy to analyze Ab:HA complexes and map how β-hairpin recognition depends on IGHV1-2 germline residues.
• The result: Displaying the β-hairpin epitope in an immunogen might reliably elicit broadly protective influenza antibodies in most humans, consistent with the 75% allele frequency.

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