Is Omicron variant XBB.1.5’s superior binding causing higher transmissibility?

Subject :Science and Technology

Context:

The XBB.1.5 Omicron recombinant variant that was first detected in the U.S. (New York and Connecticut) in late October 2022 has now spread to at least 29 countries.

XXB.1.5 variant:

The XBB.1.5 variant is a descendant of XBB.1, which, in turn, descends from XBB.
The XBB variant evolved through the recombination of two descendants of the earlier Omicron BA.2 variant.
The XBB.1.5 variant was first found in India on December 30 last year, and as per INSACOG five XBB.1.5 variants have been detected so far — three cases in Gujarat and one each in Karnataka and Rajasthan.
If XBB and XBB.1 already had high transmissibility and higher immune escape, the XBB.1.5 variant is even more transmissible while retaining significant immune escape ability.
Both XBB.1 and XBB.1.5 “significantly” evaded convalescent plasma samples from BA.1, BA.5, and BF.7 breakthrough infections.
However, XBB.1.5 displayed a slightly weaker immune evasion capability compared with XBB.1.

Transmissibility:

XBB.1.5 is the most transmissible variant that has been detected yet.
The reason for the high transmissibility of XBB.1.5 is the mutations within this recombinant sub-variant of Omicron.
The underlying mechanism for such high transmissibility remains unclear.
The additional mutation found on XBB.1.5 renders the virus with substantially higher binding affinity with the receptor compared with BQ.1.1 and XBB/XBB.1.
And compared with XBB.1, the XBB.1.5 variant has comparable antibody evasion but displays distinct transmissibility suggesting that enhanced receptor-binding affinity would indeed lead to higher growth advantages.
With a stronger immune escape ability than BQ.1.1 but limited by weaker binding affinity, XBB and XBB.1 were recorded only in a few countries. In contrast, with enhanced receptor-binding affinity but comparable antibody evasion, the prevalence of XBB.1.5 demonstrates that receptor-binding affinity will affect transmissibility.

Rare mutation of XXB.1.5:

The additional mutation seen on XBB.1.5 is the S486P on the spike protein.
The mutations at 486 reduce ACE2 [binding] affinity.
The XBB.1.5 variant fixed the reduced binding affinity seen in XBB and XBB.1 by undergoing changes in two nucleotides to become S486P.
XBB.1.5’s hACE2 binding affinity is almost comparable to that of BA.2.75, which may enable XBB.1.5 to gain more mutations, similar to what BA.2.75 had.