The BQ.1 lineages are descendants of BA.5, whereas the XBB lineage is the recombinant of two highly diversified BA.2 lineages.
At the end of 2022, the XBB.1.5 variant, a descendant of XBB.1 that acquired the S:S486P substitution, emerged and is rapidly spreading in the USA (appendix pp 6–7), and is the latest variant of concern.
Although the features of XBB.1.5 were reported by Yue and colleagues,
a comprehensive understanding of the virological characteristics of newly emerging variants is needed for sustained global health. Our epidemic dynamics analysis (appendix pp 6–7) revealed that the relative effective reproduction number (Re) of XBB.1.5 is 1·2 times greater than that of the parental XBB.1, and XBB.1.5 is outcompeting BQ.1.1, the predominant lineage in the USA as of December, 2022 (appendix pp 6–7). Our data suggest that XBB.1.5 will rapidly spread worldwide in the near future (appendix pp 6–7).
we hypothesised that the reversion of S:Y144del (ins144Y) affects the virological features of XBB.1.5. However, XBB.1.5 without S:Y144del (XBB.1.5 + ins144Y) exhibited a lower Re compared with the original XBB.1.5 (appendix pp 6–7). Lentivirus-based pseudovirus assays showed that the 144Y insertion increased the infectivity of XBB.1 but did not affect the infectivity of XBB.1.5 (appendix pp 6–7). Additionally, neutralisation assays showed that the 144Y insertion significantly increased the sensitivity to BA.2 and BA.5 breakthrough infection sera (appendix pp 6–7). Altogether, our data suggest that the reversion of S:Y144del does not improve the viral properties of XBB.1.5, including fitness.
In summary, our results suggest that XBB.1.5 is the most successful XBB lineage as of January, 2023, as it has acquired the S:S486P substitution, which enhances its binding affinity to the ACE2 receptor without compromising its remarkable immune resistance. Our data suggest that these virological features result in greater transmissibility.
We declare no competing interests. KU and JI contributed equally.
Supported in part by AMED SCARDA Japan Initiative for World-leading Vaccine Research and Development Centers UTOPIA (JP223fa627001, to KS), AMED SCARDA Program on R&D of new generation vaccine including new modality application (JP223fa727002, to Kei Sato); AMED Research Program on Emerging and Re-emerging Infectious Diseases (JP22fk0108146, to Kei Sato; JP21fk0108494 to G2P-Japan Consortium and Kei Sato; JP21fk0108425, to Kei Sato; JP21fk0108432, to Kei Sato); AMED Research Program on HIV/AIDS (JP22fk0410039, to Kei Sato); JST PRESTO (JPMJPR22R1, to Jumpei Ito); JST CREST (JPMJCR20H4, to Kei Sato); JSPS KAKENHI Grant-in-Aid for Early-Career Scientists (20K15767, Jumpei Ito); JSPS Core-to-Core Program (A. Advanced Research Networks) (JPJSCCA20190008, Kei Sato); JSPS Research Fellow DC2 (22J11578, to Keiya Uriu); The Tokyo Biochemical Research Foundation (to Kei Sato); and the project of National Institute of Virology and Bacteriology, Programme EXCELES, funded by the European Union, Next Generation EU (LX22NPO5103, to Jiri Zahradnik).
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Published: January 31, 2023
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