SARS-CoV-2 ο株 BQ.1.1 について

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BQ.1.1 についてのラモス@ramos262740691さんの考察
途中で

***超重要***
1つ目、かなり大事な情報です。
ACE2もTMPRSSも発現量の低いIGROV-1という子宮癌から樹立された細胞株(初耳っすわ)、これがオミクロン感染成立しやすい。
「何故かは分からん、これから研究やね」と筆者

と書かれてるのがあるので、超難しくても、なんとか喰らいついて読んでいく
生物学とかやってない自分にとっては
「IGROV-1」
って何？！なんだけど、どうやらココが肝らしいので、あとは独学で頑張ろう

◆mRNA bivalent booster enhances neutralization against BA.2.75.2 and BQ.1.1【bioRxiv　2022年11月1日】

Abstract

The emergence of the highly divergent SARS-CoV-2 Omicron variant has jeopardized the efficacy of vaccines based on the ancestral spike. The bivalent COVID-19 mRNA booster vaccine within the United States is comprised of the ancestral and the Omicron BA.5 spike. Since its approval and distribution, additional Omicron subvariants have been identified with key mutations within the spike protein receptor binding domain that are predicted to escape vaccine sera. Of particular concern is the R346T mutation which has arisen in multiple subvariants, including BA.2.75.2 and BQ.1.1. Using a live virus neutralization assay, we evaluated serum samples from individuals who had received either one or two monovalent boosters or the bivalent booster to determine neutralizing activity against wild-type (WA1/2020) virus and Omicron subvariants BA.1, BA.5, BA.2.75.2, and BQ.1.1. In the one monovalent booster cohort, relative to WA1/2020, we observed a reduction in neutralization titers of 9-15-fold against BA.1 and BA.5 and 28-39-fold against BA.2.75.2 and BQ.1.1. In the BA.5-containing bivalent booster cohort, the neutralizing activity improved against all the Omicron subvariants. Relative to WA1/2020, we observed a reduction in neutralization titers of 3.7- and 4-fold against BA.1 and BA.5, respectively, and 11.5- and 21-fold against BA.2.75.2 and BQ.1.1, respectively. These data suggest that the bivalent mRNA booster vaccine broadens humoral immunity against the Omicron subvariants.

◆Substantial Neutralization Escape by the SARS-CoV-2 Omicron Variant BQ.1.1【bioRxiv　2022年11月2日】

ABSTRACT

Omicron BA.5 has been the globally dominant SARS-CoV-2 variant and has demonstrated substantial neutralization escape compared with prior variants. Additional Omicron variants have recently emerged, including BA.4.6, BF.7, BA.2.75.2, and BQ.1.1, all of which have the Spike R346T mutation. In particular, BQ.1.1 has rapidly increased in frequency, and BA.5 has recently declined to less than half of viruses in the United States. Our data demonstrate that BA.2.75.2 and BQ.1.1 escape NAbs induced by infection and vaccination more effectively than BA.5. BQ.1.1 NAb titers were lower than BA.5 NAb titers by a factor of 7 in two cohorts of individuals who received the monovalent or bivalent mRNA vaccine boosters. These findings provide the immunologic context for the rapid increase in BQ.1.1 prevalence in regions where BA.5 is dominant and have implications for both vaccine immunity and natural immunity.

Omicron BA.5 has been the globally dominant SARS-CoV-2 variant1 and has demonstrated substantial neutralization escape compared with prior variants2,3. Additional Omicron variants have recently emerged, including BA.4.64, BF.7, BA.2.75.2, and BQ.1.1, all of which have the Spike R346T mutation (Fig. 1A). In particular, BQ.1.1 has rapidly increased in frequency (Fig. S1), and BA.5 has recently declined to less than half of viruses in the United States. The ability of BQ.1.1 to evade NAbs induced by vaccination and infection has not yet been determined.


We first assessed NAb titers in 16 individuals who were vaccinated and boosted with the monovalent mRNA BNT162b2 vaccine in 2021; participants were excluded from this group if they had known SARS-CoV-2 infection or a positive nucleocapsid serology (Table S1). Following the boost, median NAb titers to WA1/2020, BA.5, BF.7, BA.2.75.2, and BQ.1.1 were 45,695, 887, 595, 387, and 261, respectively (Fig. 1B). Median BQ.1.1 NAb titers were lower than median WA1/2020 and BA.5 NAb titers by factors of 175 and 3, respectively.

We next evaluated NAb titers in 15 individuals who received the monovalent mRNA boosters and in 18 individuals who received the bivalent mRNA boosters in 2022, most of whom received 3 (range 2-4) prior COVID-19 vaccine doses (Table S1). In these cohorts, 33% had documented SARS-CoV-2 Omicron infection, but we suspect that the majority were likely infected. Prior to boosting, WA1/2020 and Omicron NAb titers were higher in these groups (Fig. 1C, D) than in the uninfected 2021 cohort (Fig. 1B). Following the boost, median NAb titers to WA1/2020, BA.5, BF.7, BA.2.75.2, and BQ.1.1 were 21,507, 2829, 2276, 745, and 406, respectively, for the monovalent boosters (Fig. 1C) and were 40,515, 3693, 2399, 883, and 508, respectively, for the bivalent boosters (Fig. 1D). Median BQ.1.1 NAb titers were lower than median WA1/2020 and BA.5 NAb titers by factors of 53-80 and 7, respectively.

Our data demonstrate that BA.2.75.2 and BQ.1.1 escape NAbs induced by infection and vaccination more effectively than BA.5. BQ.1.1 NAb titers were lower than BA.5 NAb titers by a factor of 7 in two cohorts of individuals who received the monovalent or bivalent mRNA vaccine boosters. These findings provide the immunologic context for the rapid increase in BQ.1.1 prevalence in regions where BA.5 is dominant and have implications for both vaccine immunity and natural immunity. The incorporation of the R346T mutation into multiple new SARS-CoV-2 variants suggests convergent evolution.

◆Low neutralization of SARS-CoV-2 Omicron BA.2.75.2, BQ.1.1, and XBB.1 by 4 doses of parental mRNA vaccine or a BA.5-bivalent booster【bioRxiv　2022年11月4日】

Abstract

The newly emerged SARS-CoV-2 Omicron BQ.1.1, XBB.1, and other sublineages have accumulated additional spike mutations that may affect vaccine effectiveness. Here we report neutralizing activities of three human serum panels collected from individuals 1-3 months after dose 4 of parental mRNA vaccine (post-dose-4), 1 month after a BA.5-bivalent-booster (BA.5-bivalent-booster), or 1 month after a BA.5-bivalent-booster with previous SARS-CoV-2 infection (BA.5-bivalent-booster-infection). Post-dose-4 sera neutralized USA-WA1/2020, BA.5, BF.7, BA.4.6, BA.2.75.2, BQ.1.1, and XBB.1 SARS-CoV-2 with geometric mean titers (GMTs) of 1533, 95, 69, 62, 26, 22, and 15, respectively; BA.5-bivalent-booster sera improved the GMTs to 3620, 298, 305, 183, 98, 73, and 35; BA.5-bivalent-booster-infection sera further increased the GMTs to 5776, 1558,1223, 744, 367, 267, and 103. Thus, although BA.5-bivalent-booster elicits better neutralization than parental vaccine, it does not produce robust neutralization against the newly emerged Omicron BA.2.75.2, BQ.1.1, and XBB.1. Previous infection enhances the magnitude and breadth of BA.5-bivalent-booster-elicited neutralization.

◆Resistance of Omicron subvariants BA.2.75.2, BA.4.6 and BQ.1.1 to neutralizing antibodies【bioRxiv　2022年11月17日】

Abstract

Convergent evolution of SARS-CoV-2 Omicron BA.2, BA.4 and BA.5 lineages has led to the emergence of several new subvariants, including BA.2.75.2, BA.4.6. and BQ.1.1. The subvariants BA.2.75.2 and BQ.1.1 are expected to become predominant in many countries in November 2022. They carry an additional and often redundant set of mutations in the spike, likely responsible for increased transmissibility and immune evasion. Here, we established a viral amplification procedure to easily isolate Omicron strains. We examined their sensitivity to 6 therapeutic monoclonal antibodies (mAbs) and to 72 sera from Pfizer BNT162b2-vaccinated individuals, with or without BA.1/BA.2 or BA.5 breakthrough infection. Ronapreve (Casirivimab and Imdevimab) and Evusheld (Cilgavimab and Tixagevimab) lost any antiviral efficacy against BA.2.75.2 and BQ.1.1, whereas Xevudy (Sotrovimab) remained weakly active. BQ.1.1 was also resistant to Bebtelovimab. Neutralizing titers in triply vaccinated individuals were low to undetectable against BQ.1.1 and BA.2.75.2, 4 months after boosting. A BA.1/BA.2 breakthrough infection increased these titers, which remained about 18-fold lower against BA.2.75.2 and BQ.1.1, than against BA.1. Reciprocally, a BA.5 breakthrough infection increased more efficiently neutralization against BA.5 and BQ.1.1 than against BA.2.75.2. Thus, the evolution trajectory of novel Omicron subvariants facilitated their spread in immunized populations and raises concerns about the efficacy of most currently available mAbs.

Introduction

Successive sub-lineages of Omicron have spread worldwide since the identification of BA.1 in November 2021 1,2. Probably more than 80% of the population were infected by one or another Omicron subvariant in less than one year 34, without efficient protection against infection conferred by vaccination 567. The incidence of breakthrough infections in vaccinated individuals has thus increased with Omicron 83. All Omicron lineages exbibit considerable immune evasion properties. BA.1 and BA.2 contained about 32 changes in the spike protein, promoting immune escape and high transmissibility 91011. BA.5 was then predominant in many countries by mid-2022 and was responsible for a novel peak of contaminations 212. BA.4 and BA.5 bear the same spike, with 4 additional modifications when compared to BA.2. The neutralizing activity of sera from COVID-19 vaccine recipients was further reduced against BA.4/BA.5 by about 3-5 fold compared to BA.1 and BA.2 13,141516. Novel sub-variants with enhanced transmissibility rates, derived from either BA.2 or BA.4/BA.5, rapidly emerged and should become prevalent in November 2022. Their geographical distribution is heterogeneous, but they carry an additional limited set of mutations in the spike. For instance, BA.2.75.2, derived from BA.2, was first noted in India and Singapore and comprises R346T, F486S and D1199N substitutions 17-19. BA.4.6 was detected in various countries, including USA and UK, and carries R346T and N658S mutations 2021. As of November 2022, BQ.1.1 became the main circulating lineage in many countries. It also carries the R346T mutation found in BA.2.75.2, along with K444T and N460K substitutions 22. The R346T mutation has been associated with escape from monoclonal antibodies (mAbs) and from vaccine-induced antibodies 191823. This convergent evolution of the spike suggests that the different circulating SARS-CoV-2 sub-lineages faced a similar selective pressure, probably exerted by preexisting or imprinted immunity 2324. A characterization of these new viruses is needed to evaluate their potential impact.

A few recent articles and preprints reported an extensive escape of these Omicron subvariants to neutralization, studying sera from individuals who received three or four vaccine doses, including a bivalent booster 252617,27. Most of these studies were performed with lentiviral or VSV pseudotypes. In one preprint 17, recombinant SARS-CoV-2 viruses carrying spikes from Omicron sublineages in an ancestral SARS-CoV-2 backbone were generated, but they might behave somewhat differently than authentic isolates.

Here, we identified and used a highly permissive cell line to amplify BA.2.75.2, BA.4.6. and BQ.1.1 isolates. We analyzed the sensitivity of these strains to approved mAbs, to sera from Pfizer BNT162b2 vaccine recipients, and to individuals with BA.1/BA.2 or BA.5 breakthrough infections.