最近になって新たに出現した変異株 BA.2.75 にギリシャ神話から採った
『ケンタウロス』
という名前が付けられてるようですが、これからまだまだ出てくるであろう新しい変異株は強力なのばかりになりそうだから、もういっそのこと世界中の神話から強そうなヤツの名前を借りて名付けたらエエんでね・・・?
Based on sustained logistic growth in frequency in India, we've designed @PangoNetwork lineage BA.2.75 as clade 22D, labeled as "22D (Omicron)" to denote it still being considered as "Omicron variant" by @WHO. 1/4 pic.twitter.com/xuWUJ1MLud
— Nextstrain (@nextstrain) July 22, 2022
Lineage BA.2.75 / clade 22D has been growing in frequency at a rate of 0.12 per day in India, which is equivalent to initial growth of BA.5 in the US and the UK, and is now outcompeting BA.5 in India. 2/4 pic.twitter.com/J4IMw2aVYo
— Nextstrain (@nextstrain) July 22, 2022
These growth dynamics, along with mutational profile, strongly suggest this clade will spread widely, though it may not ultimately displace BA.5 viruses globally. Further rationale for decision to designate this clade can be found here: https://t.co/3YzQ2DFtCN 3/4
— Nextstrain (@nextstrain) July 22, 2022
Additionally, we've updated Nextclade at https://t.co/6ZJOIqCumR to appropriately call clade 22D viruses. 4/4 pic.twitter.com/EAL1uXbCyG
— Nextstrain (@nextstrain) July 22, 2022
https://covariants.org/variants/22D.Omicron
🎉https://t.co/wVE7ubYBoy Update!🎉
22D (BA.2.75) is now available on CoVariants! It's visible as part of Per Country & Per Variant plots, on the shared mutation page – and of course, has a page of its own!
1/8#BA275 #centaurus https://t.co/0h04ZRfG1F pic.twitter.com/DcHRGg69T4
— Dr Emma Hodcroft (@firefoxx66) July 27, 2022
This is in line with the recent addition of 22D (BA.2.75) as a @nextstrain clade – read more on that below! 👇🏻
— Dr Emma Hodcroft (@firefoxx66) July 27, 2022
On the 22D page, you can read about some initial 22D / BA.2.75 work on things like immune-evasion, see a list of defining mutations, a plot of the variant growth, link to Aquaria protein viz, & see a list of other mutations present in the variant.
3/8https://t.co/0h04ZRgdRd pic.twitter.com/aJi2Jp5xHK
— Dr Emma Hodcroft (@firefoxx66) July 27, 2022
There's also a link to the 22D / BA.2.75 @nextstrain focal build: https://t.co/lzgKAj87j4
Here, we can zoom in on the clade & get a closer look at how 22D sequences are distributed around the world, & their diversity.
4/8 pic.twitter.com/7xiDrPfTsm
— Dr Emma Hodcroft (@firefoxx66) July 27, 2022
On the Per Country page, 22D / BA.2.75 is currently only readily visible in India, where it likely originated & is most common, as well as a little in Japan. Over the next few weeks, it'll be possible to see if it grows in other countries.
5/8https://t.co/2MEeLELith pic.twitter.com/4dFQEUDRgO
— Dr Emma Hodcroft (@firefoxx66) July 27, 2022
Finally, on the Shared Mutations page (very hard to capture in a picture now, with the Omicrons!), you can see how 22D's / BA.2.75's Spike mutations compare to other VoC, including its Omicron siblings.
6/8https://t.co/Ed1gNwRnA5 pic.twitter.com/ddNry6mZ8A
— Dr Emma Hodcroft (@firefoxx66) July 27, 2022
More information on 22D / BA.2.75 will become available in due course.
As always, https://t.co/wVE7ubYBoy is open-source & we welcome your PRs & suggestions to add more studies & information to variant pages! (Or any error-catching!)https://t.co/RkMjEhTRoC7/8
— Dr Emma Hodcroft (@firefoxx66) July 27, 2022
As before, I've created a file for 22D / BA.2.75 mapping all defining mutations (relative to ancestral), including nuc->AA. This is available on CoV github!
Huge 🙏🏻 to all who helped check it! (Esp @DoktorYak & Anna N!) (Further feedback welcome!)https://t.co/TXqEKA2xcl
8/8 pic.twitter.com/KW1XyivSgG
— Dr Emma Hodcroft (@firefoxx66) July 27, 2022
抗体治療薬 bebtelovimab ――日本はキープできてんのかな?
岸田内閣のグズっぷりを見るとなぁ・・・
BA.2.75について。まだ3報しか読んでません。
免疫回避はBA.5程度でbebtelovimabがまだ効きそうなのは朗報。https://t.co/urn9KwvY2A
— ramos2 (@ramos262740691) July 27, 2022
こんな感じね。
因みに下段に感染者血漿による中和もあるんだけど、BA.5と同じくらい免疫回避する。 pic.twitter.com/ICrBst6mur— ramos2 (@ramos262740691) July 27, 2022
Cilgavimabも生き残ってそう?って思った?
いやいやこっちの論文だときついのでは。https://t.co/vSUkhvPFYm
— ramos2 (@ramos262740691) July 27, 2022
つーわけで、2報まとめるなら、とりあえずbebtelovimab一択。 pic.twitter.com/OBR2K3mJIi
— ramos2 (@ramos262740691) July 27, 2022
ACE2へのaffinityはBA.2の3倍。
R493QとN460Kによる親和性アップによるもの。https://t.co/fpNcRzQgHS
— ramos2 (@ramos262740691) July 27, 2022
こんな感じね(左図)。
彼らの実験系では以前、BA.5のACE2親和性は高くないという結果が出ています(右図)。δもね。とすると、BA.2.75の1つの懸念点は、その圧倒的なACE2親和性の高さ→病原性アップの懸念 pic.twitter.com/MXorIPAw6F
— ramos2 (@ramos262740691) July 27, 2022
彼らの論文は面白くて、BA.2.75の免疫回避能力は主にGroupAエピトープに対する免疫回避としています。
逆にBA.5は486,487のBとL452R含むD1への免疫回避能。つまり、血漿で見たときは総論としてBA.5と同程度の免疫回避力なんだけど、中身は違うのでBA.5への免疫は役に立ちにくいだろうね。 pic.twitter.com/twgMUMze3t
— ramos2 (@ramos262740691) July 27, 2022
つまりまだ3報くらいしかない現段階で分かるのは以下
・ACE2親和性は過去最強レベル?→病原性への不安
ただし、ACE2親和性はラボによって変わったことあるので一応別ラボ結果待ちたい。・免疫回避はBA.5程度。充分嫌です。が、BA.5大幅超えではなさげ。
・抗体治療薬はbebtelovimab一択
— ramos2 (@ramos262740691) July 27, 2022
ちなみにもっと読んでよと思われてもまだプレプリントざっと見3報くらいしかなく。
ニュースが言ってる感染速度3倍ってACE2親和性から来てるならだいぶ言葉が違うな…と思っている。さすがに後3-5報くらいはラボ待ちです。epidemiology速報一報、臨床速報一報は欲しいとこ。
— ramos2 (@ramos262740691) July 27, 2022
あ、ニュースが言ってる3.24倍の拡散速度は論文じゃなくTwitter由来なのね(もっと正確にはCovspectrum)。
これか。https://t.co/rxUXWO2fD8— ramos2 (@ramos262740691) July 27, 2022
Greater than Titan!
Seems like BA.2.75 has the potential to outcompete BA.5*/BA.4* and other circulating BA.2 lineages
Early days but growth advantage will be clear in a couple of weeks. pic.twitter.com/rEWqJF1T2T
— Raj Rajnarayanan (@RajlabN) July 1, 2022
◆Evasion of neutralizing antibodies by Omicron sublineage BA.2.75【bioRxiv 2022年7月20日】
Abstract
Towards the end of 2021, SARS-CoV-2 vaccine effectiveness was threatened by the emergence of the Omicron clade (B.1.1.529), with more than 30 mutations in spike. Recently, several sublineages of Omicron, including BA.2.12.1, BA.4, and BA.5, have demonstrated even greater immune evasion, and are driving waves of infections across the globe.
One emerging sublineage, BA.2.75, is increasing in frequency in India and has been detected in at least 15 countries as of 19 July 2022. Relative to BA.2, BA.2.75 carries nine additional mutations in spike. Here we report the sensitivity of the BA.2.75 spike to neutralization by a panel of clinically-relevant and pre-clinical monoclonal antibodies, as well as by serum from blood donated in Stockholm, Sweden, before and after the BA.1/BA.2 infection wave.
BA.2.75 does not show greater immune evasion than the currently-dominating BA.5 in our set of serum samples, and exhibits moderate susceptibility to tixagevimab and cilgavimab that form a widely used monoclonal antibody cocktail (Evusheld).
◆Neutralization sensitivity of Omicron BA.2.75 to therapeutic monoclonal antibodies【bioRxiv 2022年7月15日】
Abstract
Since the end of 2021, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant outcompeted other variants and took over the world. After the emergence of original Omicron BA.1, Omicron BA.2 subvariant emerged and outcompeted BA.1. As of July 2022, some BA.2 subvariants, including BA.2.12.1, BA.4 and BA.5, emerged in multiple countries and begun outcompeting original BA.2. Moreover, a novel BA.2 subvariant, BA.2.75, was detected in eight countries including India at the end of June 2022, and preliminary investigations suggest that BA.2.75 is more transmissible over the other BA.2 subvariants. On July 7, 2022, the WHO classified BA.2.75 as a variant-of-concern lineage under monitoring. We have recently demonstrated that BA.4/5 is highly resistant to a therapeutic monoclonal antibody, cilgavimab, than BA.2. The resistance of SARS-CoV-2 variants to therapeutic antibodies can be attributed to the mutations in the viral spike protein. Compared to the BA.2 spike, BA.2.12.1 and BA.4/5 respectively bear two and four mutations in their spike proteins. On the other hand, the majority of BA.2.75 spike bears nine substitutions. The fact that the mutation number in the BA.2.75 spike is larger than those in the BA.4/5 spike raises the possibility that the BA.2.75 spike significantly reduces sensitivity towards therapeutic monoclonal antibodies than BA.2 and BA.4/5. In this study, we generated pseudoviruses harboring the spike proteins of BA.2.75, BA.4/5 and BA.2 and evaluated the efficacy of ten therapeutic monoclonal antibodies and three antibody cocktails against BA.2.75.
◆Neutralizing antibody evasion and receptor binding features of SARS-CoV-2 Omicron BA.2.75【bioRxiv 2022年7月19日】
Abstract
The Omicron subvariants BA.2.75 is rapidly raising in India. BA.2.75 also shows a local growth advantage compared to BA.2.38 and BA.4/BA.5. Its immune evasion capability and receptor binding affinity is unclear and requires investigation. Here, we show that BA.2.75 is more neutralization evasive than BA.2.12.1 against the plasma from post-vaccination BA.2 infection, but less compared to BA.4/BA.5. However, as shown in a small sample of plasma from post-vaccination Delta infection, BA.2.75 seems to be more immune evasive than BA.4/BA.5 in Delta-stimulated immune background, which may explain BA. 2.75’s growth advantage over BA.4/BA.5 in India. The additional N460K, G446S, D339H and R493Q mutations carried by BA.2.75 allows it to escape BA.2-effective neutralizing antibodies of different RBD epitopes, and BA.2.75 has a distinct antibody escaping profile from BA.4/BA.5. Compared to BA.2, REGN10933 and COV2-2196 partially recovered neutralization against BA.2.75 due to R493Q reversion. However, the efficacy of their corresponding cocktail was not significantly changed, since REGN10987 and COV2-2130 showed reduced neutralizing activity due to G446S. BA.2.75 exhibits higher ACE2-binding affinity than BA.4/BA.5, which should be contributed by R493Q and N460K, according to deep mutational scanning (DMS) results. This affinity-strengthening feature is being further examined and verified, which will be updated soon.