tetano
Editor, Senior Moderator
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[SUP] 1 [/SUP], John P Evans[SUP] 2 [/SUP], Yi-Min Zheng[SUP] 1 [/SUP], Claire Carlin[SUP] 3 [/SUP], Linda J Saif[SUP] 4 [/SUP], Eugene M Oltz[SUP] 5 [/SUP], Kai Xu[SUP] 1 [/SUP], Richard J Gumina[SUP] 6 [/SUP], Shan-Lu Liu[SUP] 7 [/SUP]
Affiliations
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.
. 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[SUP] 1 [/SUP], John P Evans[SUP] 2 [/SUP], Yi-Min Zheng[SUP] 1 [/SUP], Claire Carlin[SUP] 3 [/SUP], Linda J Saif[SUP] 4 [/SUP], Eugene M Oltz[SUP] 5 [/SUP], Kai Xu[SUP] 1 [/SUP], Richard J Gumina[SUP] 6 [/SUP], Shan-Lu Liu[SUP] 7 [/SUP]
Affiliations
- PMID: 36240764
- PMCID: PMC9515334
- DOI: 10.1016/j.chom.2022.09.015
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.