PT  - JOURNAL ARTICLE
AU  - Yue, Can
AU  - Song, Weiliang
AU  - Wang, Lei
AU  - Jian, Fanchong
AU  - Chen, Xiaosu
AU  - Gao, Fei
AU  - Shen, Zhongyang
AU  - Wang, Youchun
AU  - Wang, Xiangxi
AU  - Cao, Yunlong
TI  - Enhanced transmissibility of XBB.1.5 is contributed by both strong ACE2 binding and antibody evasion
AID  - 10.1101/2023.01.03.522427
DP  - 2023 Jan 01
TA  - bioRxiv
PG  - 2023.01.03.522427
4099  - http://biorxiv.org/content/early/2023/01/05/2023.01.03.522427.short
4100  - http://biorxiv.org/content/early/2023/01/05/2023.01.03.522427.full
AB  - SARS-CoV-2 recombinant subvariant XBB.1.5 is growing rapidly in the United States, carrying an additional Ser486Pro substitution compared to XBB.1 and outcompeting BQ.1.1 and other XBB sublineages. The underlying mechanism for such high transmissibility remains unclear. Here we show that XBB.1.5 exhibits a substantially higher hACE2-binding affinity compared to BQ.1.1 and XBB/XBB.1. Convalescent plasma samples from BA.1, BA.5, and BF.7 breakthrough infection are significantly evaded by both XBB.1 and XBB.1.5, with XBB.1.5 displaying slightly weaker immune evasion capability than XBB.1. Evusheld and Bebtelovimab could not neutralize XBB.1/XBB.1.5, while Sotrovimab remains weakly reactive and notably, SA55 is still highly effective. The fact that XBB.1 and XBB.1.5 showed comparable antibody evasion but distinct transmissibility suggests enhanced receptor-binding affinity would indeed lead to higher growth advantages. The strong hACE2 binding of XBB.1.5 could also enable its tolerance of further immune escape mutations, which should be closely monitored.Competing Interest StatementY.C. is a co-founder of Singlomics Biopharmaceuticals and inventor of provisional patents associated with SARS-CoV-2 neutralizing antibodies, including SA55 and SA58. All other authors declare no competing interests.