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. 2023 Jan 31;23(3):280–281. doi: 10.1016/S1473-3099(23)00051-8

Enhanced transmissibility, infectivity, and immune resistance of the SARS-CoV-2 omicron XBB.1.5 variant

Keiya Uriu a,d, Jumpei Ito a, Jiri Zahradnik e,f, Shigeru Fujita a,d, Yusuke Kosugi a,d, Gideon Schreiber e; The Genotype to Phenotype Japan (G2P-Japan) Consortium, Kei Sato a,b,c,d,g,h,i
PMCID: PMC9889095  PMID: 36736338

In late 2022, the SARS-CoV-2 omicron BQ.1 and XBB lineages, characterised by amino acid substitutions in the spike (S) protein that increase viral fitness, had become predominant in the western (BQ.1) and eastern (XBB) hemispheres.1, 2 The BQ.1 lineages are descendants of BA.5, whereas the XBB lineage is the recombinant of two highly diversified BA.2 lineages.2

In 2022, we elucidated the characteristics of a variety of newly emerging SARS-CoV-2 omicron subvariants.1, 2, 3, 4, 5, 6 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.7 Although the features of XBB.1.5 were reported by Yue and colleagues,8 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 next investigated the virological features of XBB.1.5. Yeast surface display assay showed that the dissociation constant value of XBB.1.5 S receptor-binding domain from the human ACE2 receptor is significantly (4·3 times) lower than that of XBB.1 S receptor-binding domain (appendix pp 6–7). Experiments using lentivirus-based pseudoviruses also showed approximately 3-fold increased infectivity of XBB.1·5 compared with XBB.1 (appendix pp 6–7). These results suggest that XBB.1.5 exhibits a remarkably strong affinity to the human ACE2 receptor, which is attributed to the S486P substitution. Moreover, neutralisation assay revealed that XBB.1.5 was robustly resistant to BA.2 breakthrough infection sera (41-fold versus B.1·1, 20-fold versus BA.2) and BA.5 breakthrough infection sera (32-fold versus B.1·1, 9·5-fold versus BA.5; appendix pp 6–7).

During investigations, we observed that a subset of the XBB.1.5 variant reverted the deletion of 144Y in S (S:Y144del; appendix pp 6–7). As we previously showed that the S:Y144del mutation confers an increased immune escape capability,2 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.

Acknowledgments

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).

Supplementary Material

Supplementary appendix
mmc1.pdf (406.7KB, pdf)

References

  • 1.Ito J, Suzuki R, Uriu K, et al. Convergent evolution of the SARS-CoV-2 Omicron subvariants leading to the emergence of BQ.1·1 variant. bioRxiv. 2022 doi: 10.1101/2022.12.05.519085. published online Dec 5. (preprint). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Tamura T, Ito J, Uriu K, et al. Virological characteristics of the SARS-CoV-2 XBB variant derived from recombination of two Omicron subvariants. bioRxiv. 2022 doi: 10.1101/2022.12.27.521986. published online Dec 27. (preprint). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Yamasoba D, Kimura I, Nasser H, et al. Virological characteristics of the SARS-CoV-2 Omicron BA.2 spike. Cell. 2022;185:2103–2115. doi: 10.1016/j.cell.2022.04.035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Yamasoba D, Kosugi Y, Kimura I, et al. Neutralisation sensitivity of SARS-CoV-2 omicron subvariants to therapeutic monoclonal antibodies. Lancet Infect Dis. 2022;22:942–943. doi: 10.1016/S1473-3099(22)00365-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Kimura I, Yamasoba D, Tamura T, et al. Virological characteristics of the SARS-CoV-2 Omicron BA.2 subvariants, including BA.4 and BA.5. Cell. 2022;185:3992–4007. doi: 10.1016/j.cell.2022.09.018. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Saito A, Tamura T, Zahradnik J, et al. Virological characteristics of the SARS-CoV-2 Omicron BA.2.75 variant. Cell Host Microbe. 2022;30:1540–1555. doi: 10.1016/j.chom.2022.10.003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.WHO XBB.1.5 rapid risk assessment. 2022. https://www.who.int/docs/default-source/coronaviruse/11jan2023_xbb15_rapid_risk_assessment.pdf?sfvrsn=73e431e8_3
  • 8.Yue C, Song W, Wang L, et al. Enhanced transmissibility of XBB.1.5 is contributed by both strong ACE2 binding and antibody evasion. bioRxiv. 2023 doi: 10.1101/2023.01.03.522427. published online Jan 5. (preprint). [DOI] [PMC free article] [PubMed] [Google Scholar]

Associated Data

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Supplementary Materials

Supplementary appendix
mmc1.pdf (406.7KB, pdf)

Articles from The Lancet. Infectious Diseases are provided here courtesy of Elsevier

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