G2P-Japan(東大・佐藤研)「オミクロン亜株XBB.1.5の性状解析」――流行拡大中の XBB.1.5株の性質解明を速報

現在日本で流行のドミナントになっているο株 BQ.1.1 から今後置き換わって再度の大流行を引き起こすことがほぼ確実な XBB.1.5 について、東大の佐藤佳教授が率いるG2P-Japanで最新の研究成果をプレプリント公表前に概略をリリースしました。

アメリカ産のオミクロン亜株 XBB.1.5、もう SARS-3 にした方がよくないかな?



Virological characteristics of the SARS-CoV-2 XBB variant derived from recombination of two Omicron subvariants【bioRxiv 2022年12月27日】


In late 2022, the SARS-CoV-2 Omicron subvariants have highly diversified, and XBB is spreading rapidly around the world. Our phylogenetic analyses suggested that XBB emerged by recombination of two co-circulating BA.2 lineages, BJ.1 and BM.1.1.1 (a progeny of BA.2.75), during the summer of 2022 around India. In vitro experiments revealed that XBB is the most profoundly resistant variant to BA.2/5 breakthrough infection sera ever and is more fusogenic than BA.2.75. Notably, the recombination breakpoint is located in the receptor-binding domain of spike, and each region of recombined spike conferred immune evasion and augmented fusogenicity to the XBB spike. Finally, the intrinsic pathogenicity of XBB in hamsters is comparable to or even lower than that of BA.2.75. Our multiscale investigation provided evidence suggesting that XBB is the first documented SARS-CoV-2 variant increasing its fitness through recombination rather than single mutations.


The SARS-CoV-2 Omicron variant is the current variant of concern since the end of 2021 (ref.1). As of December 2022, recently emerging Omicron subvariants are under convergent evolution: recently emerging variants acquired substitutions at the same residues of the spike (S) protein, such as R346, K444, L452, N460, and F486. For instance, Omicron BQ.1.1 variant, which is a descendant of Omicron BA.5 and is currently becoming predominant in the Western countries1, possesses all convergent substitutions, such as R346T, K444T, L452R, N460K, and F486V. Recent studies including ours suggested that L452R, N460K, and R346T increase the binding affinity of SARS-CoV-2 S protein to human angiotensin-converting enzyme 2 (ACE2), the receptor for viral infection, while R346T, K444T and F486V contribute to evade antiviral humoral immunity induced by vaccination and natural SARS-CoV-2 infection. Similar to the observations in BA.5 (ref.5) and BA.2.75 (ref.10), combinational substitutions in S protein (1) to evade antiviral humoral immunity in exchange for the decrease of ACE2 binding affinity (e.g., F486V) and (2) to enhance ACE2 binding affinity to compensate the decreased affinity by immune evasion substitution (e.g., L452R and N460K) has been frequently observed in recently emerging Omicron subvariants including BQ.1.1. These observations suggest that acquiring these two types of substitutions in the S protein is a trend for recently emerging Omicron subvariants to spread more efficiently than prior ones.

In addition to the diversification and subsequent convergent evolution of emerging Omicron subvariants (e.g., BQ.1.1), a recombinant variant, called XBB, has recently emerged. The Omicron XBB variant likely originated by the recombination of two BA.2 descendants, BJ.1 and BM.1.1.1 (a progeny of BA.2.75). While the BQ.1 lineage is becoming predominant in Europe, XBB has become predominant in India and Singapore and is spreading several countries. As of October 28, 2022, the WHO classifies XBB as an Omicron subvariant under monitoring. Recent studies including ours have revealed the virological features of BQ.1 (refs.2, 13, 18). However, the features of XBB, another Omicron subvariants of concern, are not fully elucidated. In this study, we elucidated the virological characteristics of XBB, particularly its transmissibility, immune resistance, ACE2 binding affinity, infectivity, fusogenicity and intrinsic pathogenicity in a hamster model.