A public broadly neutralizing antibody class targets a membrane-proximal anchor epitope of influenza virus hemagglutinin

Guthmiller, J. J.; Han, J.; Utset, H. A.; Li, L.; Lan, L. Y.-L.; Henry, C.; Stamper, C. T.; Stovicek, O.; Gentles, L.; Dugan, H. L.; Zheng, N.-Y.; Richey, S. T.; Tepora, M. E.; Bitar, D. J.; Changrob, S.; Strohmeier, S.; Huang, M.; Garcia-Sastre, A.; Nachbagauer, R.; Palese, P.; Bloom, J. D.; Krammer, F.; Coughlan, L.; Ward, A. B.; Wilson, P. C.

doi:10.1101/2021.02.25.432905

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bioRxiv · 10.1101/2021.02.25.432905

A public broadly neutralizing antibody class targets a membrane-proximal anchor epitope of influenza virus hemagglutinin

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Abstract

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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Guthmiller, J. J., Han, J., Utset, H. A., Li, L., Lan, L. Y.-L., Henry, C., Stamper, C. T., Stovicek, O., Gentles, L., Dugan, H. L., Zheng, N.-Y., Richey, S. T., Tepora, M. E., Bitar, D. J., Changrob, S., Strohmeier, S., Huang, M., Garcia-Sastre, A., Nachbagauer, R., Palese, P., Bloom, J. D., Krammer, F., Coughlan, L., Ward, A. B., Wilson, P. C.. 2021-02-27. A public broadly neutralizing antibody class targets a membrane-proximal anchor epitope of influenza virus hemagglutinin. https://doi.org/10.1101/2021.02.25.432905

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