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bioRxiv · 10.1101/2022.08.14.503921

Evasion of Neutralizing Antibody Response by the SARS-CoV-2 BA.2.75 Variant

Qu, P.·Evans, J. P.·Zheng, Y.-M.·Carlin, C.·Saif, L. J.·Oltz, E. M.·Xu, K.·Gumina, R. J.·Liu, S.-L.
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Abstract

The newly emerged BA.2.75 SARS-CoV-2 variant exhibits an alarming 9 additional mutations in its spike (S) protein compared to the ancestral BA.2 variant. Here we examine the neutralizing antibody escape of BA.2.75 in mRNA-vaccinated and BA.1-infected individuals, as well as the molecular basis underlying functional changes in the S protein. Notably, BA.2.75 exhibits enhanced neutralization resistance over BA.2, but less than the BA.4/5 variant. The G446S and N460K mutations of BA.2.75 are primarily responsible for its enhanced resistance to neutralizing antibodies. The R493Q mutation, a reversion to the prototype sequence, reduces BA.2.75 neutralization resistance. The mutational impact is consistent with their locations in common neutralizing antibody epitopes. Further, the BA.2.75 variant shows enhanced cell-cell fusion over BA.2, driven largely by the N460K mutation, which enhances S processing. Structural modeling revealed a new receptor contact introduced by N460K, supporting a mechanism of potentiated receptor utilization and syncytia formation.

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Qu, P., Evans, J. P., Zheng, Y.-M., Carlin, C., Saif, L. J., Oltz, E. M., Xu, K., Gumina, R. J., Liu, S.-L.. 2022-08-15. Evasion of Neutralizing Antibody Response by the SARS-CoV-2 BA.2.75 Variant. https://doi.org/10.1101/2022.08.14.503921

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