自然消息:新的 Omicron 子变体BA.4.5威胁 传快逃避免疫

顾汉现

译：

自然  消息  文章
消息

2022 年 4 月 15 日

新的 Omicron 子变体是一种威胁吗？以下是科学家们的观察方式  

BA.4 和 BA.5，传播快，逃避免疫   BA.4.5传快逃避免疫

在南非，一个研究人员网络正在研究新谱系 BA.4 和 BA.5 是否能逃脱 COVID-19 疫苗和先前感染的免疫力。

艾米麦克斯曼

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Tulio de Oliveira 在他的实验室里摆姿势拍照
南非斯泰伦博斯大学的 Tulio de Oliveira 团队发现了 Omicron 的 BA.4 和 BA.5 子变体。图片来源：Stefan Els/斯泰伦博斯大学

这个故事得到了普利策中心的支持。

南非西开普

图利奥·德·奥利维拉 (Tulio de Oliveira) 描述了日益壮大的 Omicron SARS-CoV-2 冠状病毒家族的两个新成员时，斑点珍珠鸡飘进了花园。被称为 BA.4 和 BA.5 的子变体现在在南非越来越流行，该病毒学家在斯泰伦博斯大学流行病应对和创新中心领导着世界上最强大的 SARS-CoV-2 基因组监测项目之一在南非。

这些病毒引起了世界卫生组织 (WHO) 的关注，因为根据实验室研究，它们的突变可能使它们能够比现有的 Omicron 版本更强烈地逃避从 COVID-19 疫苗或先前感染中获得的免疫力。然而，德奥利维拉很清楚，他并没有被 BA.4 和 BA.5 吓到。尽管在过去一个月中，子变量在南非迅速普及，但该国的 COVID-19 病例和住院率保持稳定。他也很平静，因为他以前经历过这种情况——他的团队在大流行期间也有类似的发现，并且知道演习。他说，现在，“是时候小心翼翼地工作了，但要冷静。”

为什么 Omicron 子变体的传播速度比原始版本快？

科学家们现在正在研究迄今为止在九个国家检测到的这些子变量，以确定它们的影响是否严重到足以保证干预的程度。SARS-CoV-2 在进化过程中将继续变异，但并非每个变体都具有新闻价值。为了确定什么值得关注，伦敦帝国理工学院的病毒学家温迪·巴克莱（Wendy Barclay）说，研究人员关注两个因素：“我们关心疾病严重程度的差异，我们关心逃避疫苗的变体——因为即使我们有同样严重的情况下，病例的增加仍然对生活产生很大影响。”

与此同时，研究人员正在努力解决如何公开表达他们的担忧和变体的不确定性，同时又不会引发不必要的政府政策和焦虑。去年底，当 de Oliveira 的团队发现原始 Omicron 时，包括美国和英国在内的国家对南非实施了旅行禁令。这些禁令未能阻止该变种的传播，但严重损害了本已陷入困境的南非经济。如果这种情况再次发生，de Oliveira 说，“我将停止与世界实时共享数据，但会继续与我的政府共享，以指导我们自己的反应。”

新变种
22-4 月 1 日，斯泰伦博斯 de Oliveira 团队的生物信息学家 Eduan Wilkinson 发现该中心实验室和约翰内斯堡国家传染病研究所的研究人员在他们最新一批数据中标记了几个异常的 SARS-CoV-2 基因组序列. 这些序列在编码其刺突蛋白的 SARS-CoV-2 区域有一些显着的突变。由于刺突蛋白是病毒入侵细胞的关键，威尔金森认识到迫切需要在过去几个月在该国测序的所有基因组中寻找这些突变，看看它们是否被忽视了。

2021 年 11 月，一名乘客在约翰内斯堡机场查看显示取消航班的电子航班公告牌
去年年底，南非约翰内斯堡的一名乘客正在查看一个取消航班的委员会，此前该国因 Omicron 而实施了旅行禁令。学分：菲尔 Magakoe/法新社/盖蒂

在整个周末工作，他和他的同事发现他们有。一个月前——在 3 月的第一周——BA.4 和 BA.5 序列约占南非测序的大约 500 个基因组的 5%。到 4 月的第一周，这一比例已上升到 50%。那一周，一个国际病毒分类小组确定 BA.4 和 BA.5 在 Omicron 家谱上确实是它们各自独立的谱系，并给它们起了名字。

除了来自南非的累积序列外，近两周有少量BA.4序列从博茨瓦纳、比利时、丹麦和英国上传到数据平台GISAID，BA.5也出现了来自中国、法国、德国和葡萄牙。

让 BA.4 和 BA.5 在病毒学家眼中脱颖而出的一件事是它们共有的一种称为 F486V 的氨基酸突变。它位于病毒的刺突蛋白上，靠近蛋白质与细胞上的 ACE2 受体结合的位置——这种相互作用打开了感染之门。针对 COVID-19 疫苗和先前感染 SARS-CoV-2 产生的重要抗体通过紧贴该部位来中和病毒。

快速传播的 COVID 变种可以逃避免疫反应

从去年开始，病毒学家开始在实验室实验中注意到这个点的脆弱性。例如，纽约市西奈山伊坎医学院的病毒学家 Benhur Lee 和他的同事正在帮助审查一种有前途的单克隆抗体治疗方法，方法是将其暴露于携带多种 SARS-CoV-2 刺突蛋白的人工病毒中. 只有一种版本的刺突蛋白逃避了它们的抗体。它具有与 F486V 几乎相同的突变。

当时，李松了一口气，因为这种突变在现实生活中极为罕见，这表明它以某种方式阻碍了病毒的传播。GISAID 中近 1000 万条 SARS-CoV-2 序列中只有大约 50 条含有突变，因此 Lee 确信抗体治疗仍将广泛有用。但随着 BA.4 和 BA.5 在南非的迅速崛起，似乎冠状病毒已经进化，因此突变不再阻碍它，Lee 解释说。

风险分析
世卫组织病毒学家洛伦佐·苏比西（Lorenzo Subissi）表示，该机构正在追踪这两个亚谱系。但在得出任何关于它们与其他 Omicron 变体相比是否构成额外威胁的结论之前，它需要从对人类的流行病学研究中了解更多。免疫学家还通过将 BA.4 和 BA.5 样本暴露于以前感染过 SARS-CoV-2 和接种过疫苗的人的血液中来解决免疫逃逸的问题。

“这就是为什么我们立即将样本提供给世界各地的研究人员，”de Oliveira 说。其中包括南非和英国的研究人员，以及美国国立卫生研究院和中国疾病预防控制中心的研究人员。

科学家说，Omicron 变体的边境禁令忽略了证据

在确定 BA.4 和 BA.5 之后，de Oliveira 还与南非政府和该国约 200 名研究人员组成的财团会面，以制定下一步计划。由于南非的住院人数没有增加——每天只有大约 1200 例病例——他建议政府不要制定比该国现有的更严格的指导方针。到目前为止，政府还没有改变它的规则。

德奥利维拉在向其他国家的卫生官员传达变种消息的方式上特别小心，要求他们保持警惕，同时不要触发基本上是徒劳的政策，例如旅行禁令，这可能弊大于利。“我们的压力很大，”de Oliviera 说。“当我们报道 Omicron 时，我和我的同事收到了死亡威胁。我们必须在实验室前设置安全措施。”

面对这种紧张局势，巴克莱对南非的监控工作和透明度表示赞赏。尽管今年的 SARS-CoV-2 变种导致的疾病平均不如早期版本的病毒严重，但她说这并不表明冠状病毒会继续变弱。除了获得通常的突变外，SARS-CoV-2 还可以通过重组快速进化，将一个变体的一段序列插入另一个变体的基因组中。Barclay 说，如果 Omicron 变体与不同的 SARS-CoV-2 变体重组，它可能会产生一种病毒，这种病毒既能逃避免疫，又会使人生病。“如果这些新变种是病毒变得更温和的趋势的一部分，那就太好了，但没有生物学理由相信这种情况会一直如此。”

https://www.nature.com/articles/d41586-022-01069-4



原文：

nature  news  article
NEWS
15 April 2022
Are new Omicron subvariants a threat? Here's how scientists are keeping watch
In South Africa, a network of researchers are studying whether new lineages BA.4 and BA.5 escape immunity from COVID-19 vaccines and prior infections.
Amy Maxmen
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Tulio de Oliveira posed for a portrait in his lab
Tulio de Oliveira’s team at Stellenbosch University in South Africa discovered the BA.4 and BA.5 subvariants of Omicron.Credit: Stefan Els/Stellenbosch University

This story was supported by the Pulitzer Center.

Western Cape, South Africa

Speckled guineafowl drift into the garden where Tulio de Oliveira sits as he describes two new members of the growing Omicron family of SARS-CoV-2 coronaviruses. Called BA.4 and BA.5, the subvariants are now growing in prevalence in South Africa, where the virologist leads one of the world’s strongest genomic surveillance programmes for SARS-CoV-2, at the Centre for Epidemic Response and Innovation at Stellenbosch University in South Africa.

The viruses have the attention of the World Health Organization (WHO) because, according to laboratory studies, their mutations might enable them to evade immunity gained from COVID-19 vaccines or prior infections more strongly than existing versions of Omicron. De Oliveira is clear, however, that he isn’t panicked by BA.4 and BA.5. Although the subvariants have rapidly gained ground in South Africa during the past month, rates of COVID-19 cases and hospitalizations are stable in the country. He’s also unruffled because he’s been through this before — his team has made similar discoveries during the pandemic and knows the drill. Right now, he says, “it’s just time to work carefully and diligently, but calmly.”


Why does the Omicron sub-variant spread faster than the original?

Scientists are now studying these subvariants, so far detected in nine countries, to determine whether their effect is serious enough to warrant interventions. SARS-CoV-2 will continue to mutate as it evolves, but not every variant will be newsworthy. To determine what merits attention, Wendy Barclay, a virologist at Imperial College London, says that researchers focus on two factors: “We care about a difference in disease severity, and we care about a variant that evades vaccines — because even if we have the same severity, an increase in cases still has a big impact on life.”

At the same time, researchers are grappling with how to communicate their concerns and the uncertainty about variants openly, while not provoking unnecessary government policies and anxiety. Late last year, when de Oliveira’s team detected the original Omicron, countries including the United States and the United Kingdom invoked travel bans against South Africa. The bans failed to prevent the variant’s spread, but severely damaged the already struggling South African economy. If that happens again, de Oliveira says, “I would stop sharing data in real-time with the world, but would continue sharing with my government, to guide our own response.”

The new variants
On 1 April, Eduan Wilkinson, a bioinformatician on de Oliveira’s team at Stellenbosch, saw that researchers at the centre’s lab and at the National Institute for Communicable Diseases in Johannesburg had flagged several abnormal SARS-CoV-2 genome sequences in their latest batch of data. The sequences had a few notable mutations in the region of SARS-CoV-2 that encodes its spike protein. Because the spike protein is key to the virus invading cells, Wilkinson recognized an urgent need to hunt for these mutations in all of the genomes sequenced in the country over the past few months to see if they had skirted by unnoticed.

A passenger looks at an electronic flight notice board displaying cancelled flights at an airport in Johannesburg November 2021
A passenger in Johannesburg, South Africa, looks at a board of cancelled flights late last year, after travel bans were imposed on the country because of Omicron.Credit: Phill Magakoe/AFP/Getty

Working through the weekend, he and his colleagues found that they had. A month earlier — during the first week of March — the BA.4 and BA.5 sequences comprised around 5% of the roughly 500 genomes sequenced in South Africa. By the first week of April, the portion had risen to 50%. That week, an international virus classification group determined that BA.4 and BA.5 were indeed their own separate lineages on the Omicron family tree and gave them their names.

In addition to the accumulating sequences from South Africa, a relatively small number of BA.4 sequences have been uploaded to the data platform GISAID from Botswana, Belgium, Denmark and the United Kingdom in the past two weeks, and BA.5 has shown up from China, France, Germany and Portugal.

One thing that makes BA.4 and BA.5 stand out to virologists is an amino acid mutation they share called F486V. It is located on the viruses’ spike protein near where the protein attaches to the ACE2 receptor on cells — an interaction that opens the door to infection. Important antibodies generated in response to COVID-19 vaccines and to prior infections with SARS-CoV-2 neutralize the virus by clinging to this spot.


Fast-spreading COVID variant can elude immune responses

Since last year, virologists began noticing the vulnerability of this spot in laboratory experiments. For example, virologist Benhur Lee at the Icahn School of Medicine at Mount Sinai in New York City and his colleagues were helping to vet a promising monoclonal antibody treatment by exposing it to an artificial virus carrying many versions of the SARS-CoV-2 spike protein. Only one version of the spike protein evaded their antibodies. It had a mutation nearly identical to F486V.

At the time, Lee was relieved that the mutation was vanishingly rare in real life, suggesting that it hindered the virus in some way. Only about 50 of the nearly 10 million SARS-CoV-2 sequences in GISAID contained the mutation, so Lee felt assured that the antibody treatment would still be broadly useful. But with the rapid rise of BA.4 and BA.5 in South Africa, it seems that the coronavirus has evolved so that the mutation no longer holds it back, Lee explains.

Risk analysis
Lorenzo Subissi, a virologist at the WHO, says the agency is tracking the two sub-lineages. But before it draws any conclusion about whether they pose an additional threat compared with other Omicron variants, it needs to learn more from epidemiological studies of people. Immunologists are also approaching the question of immune escape by exposing samples of BA.4 and BA.5 to blood drawn from people previously infected with SARS-CoV-2 and people who have been vaccinated.

“This is why we straight away gave samples to researchers around the world,” de Oliveira says. That included researchers in South Africa and the United Kingdom, as well as those at the US National Institutes of Health and the Chinese Center for Disease Control and Prevention.


Omicron-variant border bans ignore the evidence, say scientists

Right after identifying BA.4 and BA.5, de Oliveira also met with the South African government and a consortium of about 200 researchers in the country to strategize next steps. With no increase in hospitalizations in South Africa — and only about 1,200 cases per day — he advised the government against setting stricter guidances than the country already has. So far, the government hasn’t changed its rules.

De Oliveira was particularly careful with how he conveyed news of variants to health officials from other countries, asking them to keep watch while not triggering largely futile policies, such as travel bans, that can cause more harm than good. “We have a lot of pressure on us,” de Oliviera says. “When we reported Omicron, me and my colleagues got death threats. We had to put security in front of the lab.”

In the face of such tensions, Barclay applauds South Africa’s surveillance work and transparency. Although this year’s SARS-CoV-2 variants cause, on average, less severe disease than earlier versions of the virus, she says that’s not a sign that the coronavirus will continue to become weaker. In addition to acquiring usual mutations, SARS-CoV-2 can evolve rapidly through recombination, inserting one chunk of a sequence from a variant into the genome of another. If an Omicron variant recombines with a different SARS-CoV-2 variant, it might produce a virus that both evades immunity and makes people sicker, Barclay says. “It would be great if these new variants are part of a trend in which the virus is becoming milder, but there’s no biological reason to believe that will always be the case.”

doi: https://doi.org/10.1038/d41586-022-01069-4