Yunlong Richard Cao

Yunlong Richard Cao

31-10-2022

11:06

Latest update on some new convergent variants. Summary: 1. XBB, XBB.1, CH.1.1, BA.4.6.3, and BQ.1.1.10 (BQ.1.1+Y144del) are currently the most immune-evasive strains to monitor. 2. BQ.1*+NTD mutations, such as Y144del, makes them much more immune evasive.

Like @LongDesertTrain @JosetteSchoenma @CorneliusRoemer have mentioned, recently there has been a rapid increase of Y144del proportion in the BQ.1* lineages. This NTD deletion is observed in many worrisome BA.5 sublineages such as BQ.1.1.10, BQ.1.18, as well as BA.4.6.3.

The appearance of Y144del in those BA.5 sublineages is a really bad sign since we know this mutation is extremely good at escaping NTD-neutralizing antibodies. See below, Y144 is located at the epitope center of a specific group of NTD NAbs that are potent against BA.5.

Even worse, NTD NAbs are enriched in individuals infected or boosted with BA.2/BA.5 compared to BA.1 and WT. Indeed, BQ.1.1+Y144del (BQ.1.1.10) has greatly boosted the immune evasion capability of BQ.1.1, and is most significant in BA.5 convalescents (~3-fold).

We previously predicted that BQ.1.1* may soon gain Y144del because of the huge transmission advantage it would give, but we didn't foresee the speed.

Notably, XBB.1 (XBB + G252V) has escaped all NTD NAbs we tested. These NTD NAbs were isolated from pre-Omicron infections/vaccinations, so not clear yet how XBB.1 would impact NTD NAbs elicited by BA.5 boosting/infection (Working on it, and should soon obtain data).

Regarding the newly emerged CH.1.1 (BA.2.75 + R346T + K444T + L452R + F486S) and BA.4.6.3 (BA.4.6 + K444N + N460K + Y144del), they are both very good at escaping RBD-neutralizing antibodies. Both Evusheld and Bebtelovimab are ineffective against them.

CH.1.1 is currently the most RBD-NAbs evasive strain tested, even higher than XBB, although the difference is small. CH.1.1 is a BA.2.75 sublineage, which means it is also good at escaping NTD NAbs. This is why CH.1.1 displays such a high relative growth advantage.

Lastly, I want to emphasize that the current convergent evolution trend can be predicted. See below, the S-series pseudoviruses were predicted/constructed in July, and check how close they are to the emerging mutants. However, I thought our prediction would last till next July😂



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