RT Journal Article
SR Electronic
T1 Enhanced transmissibility of XBB.1.5 is contributed by both strong ACE2 binding and antibody evasion
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2023.01.03.522427
DO 10.1101/2023.01.03.522427
A1 Yue, Can
A1 Song, Weiliang
A1 Wang, Lei
A1 Jian, Fanchong
A1 Chen, Xiaosu
A1 Gao, Fei
A1 Shen, Zhongyang
A1 Wang, Youchun
A1 Wang, Xiangxi
A1 Cao, Yunlong
YR 2023
UL http://biorxiv.org/content/early/2023/01/05/2023.01.03.522427.abstract
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.