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Cell Host Microbe . Evasion of neutralizing antibody responses by the SARS-CoV-2 BA.2.75 variant

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  • Cell Host Microbe . Evasion of neutralizing antibody responses by the SARS-CoV-2 BA.2.75 variant


    Cell Host Microbe


    . 2022 Sep 28;S1931-3128(22)00471-1.
    doi: 10.1016/j.chom.2022.09.015. Online ahead of print.
    Evasion of neutralizing antibody responses by the SARS-CoV-2 BA.2.75 variant


    Panke Qu 1 , John P Evans 2 , Yi-Min Zheng 1 , Claire Carlin 3 , Linda J Saif 4 , Eugene M Oltz 5 , Kai Xu 1 , Richard J Gumina 6 , Shan-Lu Liu 7



    AffiliationsFree PMC article

    Abstract

    The newly emerged BA.2.75 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant contains 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 S. 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 impact of these mutations is consistent with their locations in common neutralizing antibody epitopes. Further, BA.2.75 shows enhanced cell-cell fusion over BA.2, driven largely by the N460K mutation, which enhances S processing. Structural modeling reveals enhanced receptor contacts introduced by N460K, suggesting a mechanism of potentiated receptor utilization and syncytia formation.

    Keywords: BA.2.75; Omicron; SARS-CoV-2; cell-cell fusion; mRNA booster; mRNAvaccine; neutralizing antibodies.

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