Evasion of neutralizing antibody responses by the SARS-CoV-2 BA.2.75 variant.
Cell Host Microbe
; 30(11): 1518-1526.e4, 2022 11 09.
Article
in English
| MEDLINE | ID: covidwho-2117599
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
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antibodies, Neutralizing
/
COVID-19
Topics:
Vaccines
/
Variants
Limits:
Humans
Language:
English
Journal:
Cell Host Microbe
Journal subject:
Microbiology
Year:
2022
Document Type:
Article
Affiliation country:
J.chom.2022.09.015
Similar
MEDLINE
...
LILACS
LIS