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The Sato Lab (Kei Sato) Profile picture
@SystemsVirology
Dec 5, 2022 • 9 tweets • 5 min read • Read on X
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BREAKING🔔 The 14th preprint from G2P-Japan🇯🇵 is out @biorxivpreprint. We illuminated the evolutionary rule underlying the convergent evolution of #Omicron and the virological characteristics of one of the latest lineages of concern, BQ.1.1. Please RT. 1/
biorxiv.org/content/10.110…
In late 2022, the Omicron subvariants have highly diversified. However, some lineages have convergently acquired amino acid substitutions at five critical residues in the spike protein: R346, K444, L452, N460 and F486. 2/
Omicron BQ.1.1 (aka #Cerberus), a descendant of BA.5, bears all five substitutions at the convergent sites: #R346T #K444T #L452R #N460K #F486V. 3/
Here, we, particularly two shining young talents, @jampei2 & @SpyrosLytras, performed phylogenetic and epidemic dynamics analyses and showed that Omicron subvariants independently increased their viral fitness by acquiring the convergent substitutions. 4/
All five convergent substitutions (R346T, K444T, L452R, N460K & F486V) contributed to increasing relative basic reproduction number (Re) (left), and BQ.1.1, which harbors all five convergent substitutions, showed the highest fitness among the viruses investigated (right). 5/
Neutralization assay showed that BQ.1.1 is more resistant to breakthrough BA.2/5 infection sera than BA.5. 6/
We have shown lines of data suggesting the close association of viral fusogenicity and intrinsic pathogenicity. For instance, both BA.5 (the link is shown below⬇️) and BA.2.75, descendants of BA.2, are more fusogenic and pathogenic than parental BA.2. 7/
Notably, the BQ.1.1 spike exhibited greater fusogenicity than the BA.5 spike, suggesting that BQ.1.1 is more pathogenic than BA.5. 8/
However, unexpectedly, experiments using hamsters showed that the pathogenicity of BQ.1.1 in hamsters is comparable to or even lower than that of BA.5.

Our multiscale investigations provide insights into the evolutionary trajectory of Omicron subvariants. 9/9

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More from @SystemsVirology

The Sato Lab (Kei Sato) Profile picture
Nov 21
#拡散希望 速報🔔 G2P-Japan🇯🇵の新しいプレプリント「JN.1対応mRNAワクチンが誘導する中和抗体の効果の評価」を、bioRxiv @biorxivpreprint に発表しました。1/
biorxiv.org/content/10.110…
本研究では、#ファイザー 🇺🇸🇩🇪のワクチンと、#第一三共 🇯🇵の国産ワクチンを接種した方の、ワクチン接種前後の血清を用いた検討実験を行いました。
まず朗報として、２つのワクチンで誘導される中和抗体の活性に大差はなく、どちらの血清も、JN.1のみならずKP.3.1.1やXECの感染を強く抑制しました。2/ Image
しかし、科学的観点からは、注目すべき点がふたつ。

その１。われわれは最近、JN.1やKP.3.3の「自然感染」では、強い中和抗体活性が誘導されないことを示しました。しかし上述の通り、JN.1ワクチンでは、強い中和活性（NT50; 50%中和抗体価）が誘導されています。この違いはいったい🤔？ 3/ Image
Read 9 tweets
The Sato Lab (Kei Sato) Profile picture
Nov 21
BREAKING🔔 A new study from G2P-Japan🇯🇵, led by Keiya @Keiya717, is out at @biorxivpreprint. We assessed the humoral immunity induced by JN.1 mRNA vaccines against a broad range of SARS-CoV-2 variants including JN.1, KP.3.1.1 & XEC. Please repost🔥 1/
biorxiv.org/content/10.110…
In this study, we used 2 mRNA vaccines, one is from Pfizer/BioNTech🇺🇸🇩🇪, while another is from Daiichi-Sankyo🇯🇵. The good news is that there are no significant differences between them and both broadly neutralized a variety of SARS-CoV-2 including JN.1, KP.3.1.1 and XEC. 2/ Image
But there are two scientific interests.

First, compared to our recent study using JN.1 and KP.3.3 breakthrough (i.e. natural) infection sera, antiviral humoral immunity against KP.3 and XEC was weakly induced. However, JN.1 mNRA vaccine can. Why🤔?? 3/ Image
Read 8 tweets
The Sato Lab (Kei Sato) Profile picture
Oct 17
BREAKING🔔 A new study from G2P-Japan🇯🇵, led by Yu in my lab, is out at bioRxiv @biorxivpreprint. We elucidated the virological characteristics of SARS-CoV-2 #XEC. Please repost🔥 1/
biorxiv.org/content/10.110…
Compared with KP.3, #XEC harbors two spike substitutions, S:T22N and S:F59S. Recombination analysis by Shusuke @KawakuboShusuke showed that XEC is a recombinant lineage of KS.1.1 (JN.13.1.1.1) and KP.3.3 (JN.1.11.1.3.3) with a breakpoint at genomic position 21,738–22,599. 2/ Image
Image
Transmissibility/fitness (Re):
Molecular phylogenetic-epidemic dynamics modeling led by Jumpei @jampei2 and Kaho showed that the Re of #XEC is greater than that of KP.3.1.1, the most predominant variant in the world. 3/ Image
Read 7 tweets
The Sato Lab (Kei Sato) Profile picture
Jul 17
#拡散希望 速報🔔 G2P-Japan🇯🇵の新しい研究成果「新型コロナウイルス変異株KP.3.1.1のウイルス学的特性の解明」について、プレプリント公開に先立って速報します。本研究では、最近いくつかの国で増加傾向にある、JN.1の子孫株である新しい変異株KP.3.1.1の特性を検証しました。1/
春になり、JN.1の子孫株が出現し、それらが優勢になり始めています。現在本邦は第11波に入っていますが、それはこれらのJN.1の子孫株によって引き起こされています。現在の流行状況などについては、本日公開の最新コラムで解説しています↓ 2/
そのひとつ、KP.2 (JN.1.11.1.2)については、すでにG2P-Japan🇯🇵が論文として報告しています。3/
Read 10 tweets
The Sato Lab (Kei Sato) Profile picture
Jul 17
BREAKING🔔 Here I want to quickly report our new results from G2P-Japan🇯🇵 before the preprint publication. We have elucidated the virological characteristics of SARS-CoV-2 KP.3.1.1 - a progeny of JN.1. Please RT🔥 1/
Cf.1 A new one, KP.2 (JN.1.11.1.2), has been already elucidated. 2/
Cf.2 Another new ones, KP.3 (JN.1.11.1.3), LB.1 (JN.1.9.2.1) and KP.2.3 (JN.1.11.1.2.3), have also been already elucidated. 3/
Read 8 tweets
The Sato Lab (Kei Sato) Profile picture
Jun 6
#拡散希望 速報🔔 G2P-Japan🇯🇵の新しい研究成果「新型コロナウイルス変異株KP.3, LB.1, KP.2.3のウイルス学的特性の解明」について、プレプリント公開に先立って速報します。本研究では、最近いくつかの国で増加傾向にある、JN.1の子孫株である新しい3つの変異株の特性を検証しました。1/
春になり、JN.1の子孫株が出現し、それらが優勢になり始めています。そのひとつ、KP.2 (JN.1.11.1.2)の特性については、すでにG2P-Japan🇯🇵が論文として報告しています。2/
今回着目したのは、KP.2にやや遅れて出現した3つの株、KP.3 (JN.1.11.1.3)、LB.1 (JN.1.9.2.1)、KP.2.3 (JN.1.11.1.2.3)です。それぞれ、こんな変異を持っています。
（＊参考まで、JN.1=BA.2.86.1.1で、BA.2.86系統の子孫株）3/ Image
Read 8 tweets

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