A public broadly neutralizing antibody class targets a membrane-proximal anchor epitope of influenza virus hemagglutinin
Jenna J. Guthmiller,
Henry A. Utset,
Linda Yu-Ling Lan,
Christopher T. Stamper,
Lauren E Gentles,
Haley L. Dugan,
Sara T. Richey,
Micah E. Tepora,
Dalia J. Bitar,
Rafael A. Medina,
Jesse D Bloom,
Andrew B. Ward,
Patrick C Wilson
Posted 27 Feb 2021
bioRxiv DOI: 10.1101/2021.02.25.432905
Posted 27 Feb 2021
Broadly neutralizing antibodies against influenza virus hemagglutinin (HA) have the potential to provide universal protection against influenza virus infections. Here, we report a distinct class of broadly neutralizing antibodies targeting an epitope toward the bottom of the HA stalk domain where HA is "anchored" to the viral membrane. Antibodies targeting this membrane-proximal anchor epitope utilized a highly restricted repertoire, which encode for two conserved motifs responsible for HA binding. Anchor targeting B cells were common in the human memory B cell repertoire across subjects, indicating pre-existing immunity against this epitope. Antibodies against the anchor epitope at both the serological and monoclonal antibody levels were potently induced in humans by a chimeric HA vaccine, a potential universal influenza virus vaccine. Altogether, this study reveals an underappreciated class of broadly neutralizing antibodies against H1-expressing viruses that can be robustly recalled by a candidate universal influenza virus vaccine.
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