Antibody escape mutations of SARS-CoV-2 BA.2.75 Antibody Coronavirus Disease COVID Omicron SARSCoV2 cellhostmicrobe OhioState
By Dr. Liji Thomas, MDOct 4 2022Reviewed by Benedette Cuffari, M.Sc. The coronavirus disease 2019 pandemic caused great havoc worldwide, directly through its impact on human health and because of the non-pharmaceutical measures implemented to mitigate its spread.
Introduction Among the various SARS-CoV-2 variants detected, the most notable were often immune escape variants capable of causing reinfection and breakthrough infections following natural infection and vaccination, respectively. Other variants capable of faster and wider transmission or more virulent disease have been referred to as SARS-CoV-2 variants of concern .
BA 2.75 is now spreading in Southeast Asia; however, it has also been identified in other countries worldwide. This subvariant comprises nine spike mutations, several of which reside in the receptor binding domain , which may drive its immune escape characteristics. Related StoriesConversely, one booster dose appeared to restore neutralizing capacity against Omicron, irrespective of the subvariants. However, the neutralizing response was five-fold weaker against BA.2.75 compared to D614G and four-fold weaker against BA.2 and BA.2.12.1. Despite this, BA.2.75 was neutralized more potently than BA.4 or BA.5, which showed 10-fold escape as compared to D614G.
The researchers identified the G446S and N460K mutations, as well as the reversion mutation R493Q, as responsible for enhanced nAb escape with BA.2.75 compared to BA.2. R493Q restores the neutralizing epitopes, at least in part, to the BA.2.75 compared to their loss in BA.2. Structural modeling showed the potential modes by which these key mutations affected the structure and interactions of the spike ectodomain or the RBD in the BA.2.75-receptor complex as compared to the BA.1/BA.2 spike-receptor complexes.
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