PT  - JOURNAL ARTICLE
AU  - Keiya Uriu
AU  - Jumpei Ito
AU  - Jiri Zahradnik
AU  - Shigeru Fujita
AU  - Yusuke Kosugi
AU  - Gideon Schreiber
AU  - The Genotype to Phenotype Japan (G2P-Japan) Consortium
AU  - Kei Sato
TI  - Enhanced transmissibility, infectivity and immune resistance of the SARS-CoV-2 Omicron XBB.1.5 variant
AID  - 10.1101/2023.01.16.524178
DP  - 2023 Jan 01
TA  - bioRxiv
PG  - 2023.01.16.524178
4099  - http://biorxiv.org/content/early/2023/01/17/2023.01.16.524178.short
4100  - http://biorxiv.org/content/early/2023/01/17/2023.01.16.524178.full
AB  - In 2022, we have elucidated the characteristics of a variety of newly emerging SARS-CoV-2 Omicron subvariants. At the end of 2022, the XBB.1.5 variant, an descendant of XBB.1 that acquired the S:F486P substitution, emerged and is rapidly spreading in the USA and is the latest variant of concern. Although the features of XBB.1.5 was already reported by another group as a preprint, we think multiple and independent evaluations important, and these reports are crucial for sustained global health. In this study, our epidemic dynamics analysis revealed that the relative effective reproduction number (Re) of XBB.1.5 is more than 1.2-fold 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. Our data suggest that XBB.1.5 will rapidly spread worldwide in the near future. Yeast surface display assay and pseudovirus assay respectively showed that the ACE2 binding affinity and infectivity of XBB.1.5 is 4.3-fold and 3.3-fold higher than those of XBB.1, respectively. Moreover, neutralization assay revealed that XBB.1.5 is 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), respectively. Because the immune resistance of XBB.1.5 is comparable to that of XBB.1, our results suggest that XBB.1.5 is the most successful XBB lineage as of January 2023 by acquiring the S:F486P substitution to augment ACE2 binding affinity without losing remarkable immune resistance, which leads to greater transmissibility.Competing Interest StatementThe authors have declared no competing interest.