A broad antibody class engages the influenza virus hemagglutinin head at its stem interface

Simmons, H. C.; Finney, J.; Kotaki, R.; Adachi, Y.; Moseman, A. P.; Watanabe, A.; Song, S.; Robinson-McCarthy, L. R.; Le Sage, V.; Kuraoka, M.; Moseman, E. A.; Kelsoe, G.; Takahashi, Y.; McCarthy, K. R.

doi:10.1101/2023.12.13.571543

bioRxiv · 10.1101/2023.12.13.571543

A broad antibody class engages the influenza virus hemagglutinin head at its stem interface

Simmons, H. C.·Finney, J.·Kotaki, R.·Adachi, Y.·Moseman, A. P.·Watanabe, A.·Song, S.·Robinson-McCarthy, L. R.·Le Sage, V.·Kuraoka, M.·Moseman, E. A.·Kelsoe, G.·Takahashi, Y.·McCarthy, K. R.

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Abstract

Influenza infection and vaccination impart strain-specific immunity that protects against neither seasonal antigenic variants nor the next pandemic. However, antibodies directed to conserved sites can confer broad protection. Here we identify and characterize a class of human antibodies that engage a previously undescribed, conserved epitope on the influenza hemagglutinin (HA) protein. Prototype antibody S8V1-157 binds at the normally occluded interface between the HA head and stem. Antibodies to this HA head-stem interface epitope are non-neutralizing in vitro but protect against lethal influenza infection in mice. Antibody isotypes that direct clearance of infected cells enhance this protection. Head-stem interface antibodies bind to most influenza A serotypes and seasonal human variants, and are present at low frequencies in the memory B cell populations of multiple human donors. Vaccines designed to elicit these antibodies might contribute to "universal" influenza immunity.

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Simmons, H. C., Finney, J., Kotaki, R., Adachi, Y., Moseman, A. P., Watanabe, A., Song, S., Robinson-McCarthy, L. R., Le Sage, V., Kuraoka, M., Moseman, E. A., Kelsoe, G., Takahashi, Y., McCarthy, K. R.. 2023-12-14. A broad antibody class engages the influenza virus hemagglutinin head at its stem interface. https://doi.org/10.1101/2023.12.13.571543

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