追踪新冠变异株：新冠病毒刺突蛋白Spike突变
Multiple SARS-CoV-2 variants are circulating globally. Several new variants emerged in the fall of 2020, most notably:In the United Kingdom (UK), a new variant of SARS-CoV-2 (known as 20I/501Y.V1, VOC 202012/01, or B.1.1.7) emerged with a large number of mutations. This variant has since been detected in numerous countries around the world, including the United States (US). In January 2021, scientists from UK reported evidence that suggests the B.1.1.7 variant may be associated with an increased risk of death compared with other variants. More studies are needed to confirm this finding. This variant was reported in the US at the end of December 2020.
In South Africa, another variant of SARS-CoV-2 (known as 20H/501Y.V2 or B.1.351) emerged independently of B.1.1.7. This variant shares some mutations with B.1.1.7. Cases attributed to this variant have been detected in multiple countries outside of South Africa. This variant was reported in the US at the end of January 2021.
In Brazil, a variant of SARS-CoV-2 (known as P.1) emerged that was first was identified in four travelers from Brazil, who were tested during routine screening at Haneda airport outside Tokyo, Japan. This variant has 17 unique mutations, including three in the receptor binding domain of the spike protein. This variant was detected in the US at the end of January 2021.
(1)
B.1.1.7, aka 501Y.V1 variant, 20I/501Y.V1, and UK COVID variant 英国变异株
Rambaut A, Loman N, et int., and Volz E. “Preliminary genomic characterisation of an emergent SARS-CoV-2 lineage in the UK defined by a novel set of spike mutations.” Virological.org, 2020.
(2)
B.1.351, aka 501.V2 variant, 20C/501Y.V2, and South African COVID-19 variant 南非变异株
Tegally H, Wilkinson E, et int., and de Oliveira T. “Emergence and rapid spread of a new severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) lineage with multiple spike mutations in South Africa.” medRxiv, 2020. doi.org/10.1101/2020.12.21.20248640.
(3)
P.1, aka 501Y.V3 variant, and K417T/E484K/N501Y 巴西变异株
Naveca F, Nascimento V, et int., and Bello G. “Phylogenetic relationship of SARS-CoV-2 sequences from Amazonas with emerging Brazilian variants harboring mutations E484K and N501Y in the Spike protein.” Virological.org, 2021.
新的变异株：
B.1.526 纽约变异株
SARS-CoV-2 lineage B.1.526 emerging in the New York region detected by software utility created to query the spike mutational landscape
Abstract
Wide-scale SARS-CoV-2 genome sequencing is critical to monitoring and understanding viral evolution during the ongoing pandemic. Variants first detected in the United Kingdom, South Africa, and Brazil have spread to multiple countries. We have developed a software tool, Variant Database (VDB), for quickly examining the changing landscape of spike mutations. Using this tool, we detected an emerging lineage of viral isolates in the New York region that shares mutations with previously reported variants. The most common sets of spike mutations in this lineage (now designated as B.1.526) are L5F, T95I, D253G, E484K or S477N, D614G, and A701V. This lineage appeared in late November 2020, and isolates from this lineage account for ~5% of coronavirus genomes sequenced and deposited from New York during late January 2021.
https://www.biorxiv.org/content/10.1101/2021.02.14.431043v1
CAL.20C 南加州变异株
Emergence of a novel SARS-CoV-2 strain in Southern California, USA
Abstract
Since October 2020, novel strains of SARS-CoV-2 including B.1.1.7, have been identified to be of global significance from an infection and surveillance perspective. While this strain (B.1.1.7) may play an important role in increased COVID rates in the UK, there are still no reported strains to account for the spike of cases in Los Angeles (LA) and California as a whole, which currently has some of the highest absolute and per-capita COVID transmission rates in the country. From the early days of the pandemic when LA only had a single viral genome uploaded onto GISAID we have been at the forefront of generating and analyzing the SARS-CoV-2 sequencing data from the LA region. We report a novel strain emerging in Southern California. Most current cases in the catchment population in LA fall into two distinct subclades: 1) 20G (24% of total) is the predominant subclade currently in the United States 2) a relatively novel strain in clade 20C, CAL.20C strain (∼36% of total) is defined by five concurrent mutations. After an analysis of all of the publicly available data and a comparison to our recent sequences, we see a dramatic growth in the relative percentage of the CAL.20C strain beginning in November of 2020. The predominance of this strain coincides with the increased positivity rate seen in this region. Unlike 20G, this novel strain CAL.20C is defined by multiple mutations in the S protein, a characteristic it shares with both the UK and South African strains, both of which are of significant clinical and scientific interest
https://www.medrxiv.org/content/10.1101/2021.01.18.21249786v1
Novel SARS-CoV-2 spike variant identified through viral genome sequencing of the pediatric Washington D.C. COVID-19 outbreak
https://www.medrxiv.org/content/10.1101/2021.02.08.21251344v1
L18F substrain of SARS-CoV-2 VOC-202012/01 is rapidly spreading in England
https://www.medrxiv.org/content/10.1101/2021.02.07.21251262v1
Emergence of SARS-CoV-2 stains harbouring the signature mutations of both A2a and A3 clade
https://www.medrxiv.org/content/10.1101/2021.02.04.21251117v1
Circulating SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity
Abstract: Vaccination elicits immune responses capable of potently neutralizing SARS-CoV-2. However, ongoing surveillance has revealed the emergence of variants harboring mutations in spike, the main target of neutralizing antibodies. To understand the impact of globally circulating variants, we evaluated the neutralization potency of 48 sera from BNT162b2 and mRNA-1273 vaccine recipients against pseudoviruses bearing spike proteins derived from 10 strains of SARS- CoV-2. While multiple strains exhibited vaccine-induced cross-neutralization comparable to wild- type pseudovirus, 5 strains harboring receptor-binding domain mutations, including K417N/T, E484K, and N501Y, were highly resistant to neutralization. Cross-neutralization of B.1.351 variants was weak and comparable to SARS-CoV and bat-derived WIV1-CoV, suggesting that a relatively small number of mutations can mediate potent escape from vaccine responses. While the clinical impact of neutralization resistance remains uncertain, these results highlight the potential for variants to escape from neutralizing humoral immunity and emphasize the need to develop broadly protective interventions against the evolving pandemic.
https://www.medrxiv.org/content/10.1101/2021.02.14.21251704v1
Recombination of B.1.1.7 and B.1.429 variant英美重组（杂合）变异体
The recombinant was discovered by Bette Korber at the Los Alamos National Laboratory in New Mexico, who told a meeting organised by the New York Academy of Sciences on 2 February that she had seen “pretty clear” evidence of it in her database of US viral genomes.
The hybrid virus is the result of recombination of the highly transmissible B.1.1.7 variant discovered in the UK and the B.1.429 variant that originated in California and which may be responsible for a recent wave of cases in Los Angeles because it carries a mutation making it resistant to some antibodies. It does carry a mutation from B.1.1.7, called Δ69/70, which makes the UK virus more transmissible, and another from B.1.429, called L452R, which can confer resistance to antibodies.
https://www.newscientist.com/article/2268014-exclusive-two-variants-have-merged-into-heavily-mutated-coronavirus/
Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity
https://doi.org/10.1016/j.cell.2021.03.013
Summary
Vaccination elicits immune responses capable of potently neutralizing SARS-CoV-2. However, ongoing surveillance has revealed the emergence of variants harboring mutations in spike, the main target of neutralizing antibodies. To understand the impact of these variants, we evaluated the neutralization potency of 99 individuals that received one or two doses of either BNT162b2 or mRNA-1273 vaccines against pseudoviruses representing 10 globally circulating strains of SARS-CoV-2. Five of the 10 pseudoviruses, harboring receptor-binding domain mutations, including K417N/T, E484K, and N501Y, were highly resistant to neutralization. Cross-neutralization of B.1.351 variants was comparable to SARS-CoV and bat-derived WIV1-CoV, suggesting that a relatively small number of mutations can mediate potent escape from vaccine responses. While the clinical impact of neutralization resistance remains uncertain, these results highlight the potential for variants to escape from neutralizing humoral immunity and emphasize the need to develop broadly protective interventions against the evolving pandemic.
https://www.cell.com/cell/fulltext/S0092-8674(21)00298-1 印度变异株的感染性和抗原性 （免疫逃逸能力）
1. Infectivity and antigenicity of SARS-CoV-2 B.1.617 variants
https://www.researchsquare.com/article/rs-596463/v1
SARS-CoV-2 has caused the COVID-19 pandemic. Recently, B.1.617 variants have been transmitted rapidly in India. The transmissibility, pathogenicity, and neutralization characteristics of these variants have received considerable interest. In this study, 22 pseudotyped viruses were constructed for B.1.617 variants and their corresponding single amino acid mutations. B.1.617 variants did not exhibit significant enhanced infectivity in human cells, but mutations T478K and E484Q in the receptor binding domain led to enhanced infectivity in mouse ACE2-overexpressing cells. Furin activities were slightly increased against B.1.617 variants and cell–cell fusion after infection of B.1.617 variants was enhanced. Furthermore, B.1.617 variants escaped neutralization by several mAbs, mainly because of mutations L452R, T478K, and E484Q in the receptor binding domain. The neutralization activities of sera from convalescent patients, inactivated vaccine-immunized volunteers, adenovirus vaccine-immunized volunteers, and SARS-CoV-2 immunized animals against pseudotyped B.1.617 variants were reduced by approximately twofold, compared with the D614G variant.
2. Reduced neutralization of SARS-CoV-2 B.1.617 variant by inactivated and RBD-subunit vaccine
https://doi.org/10.1101/2021.07.09.451732
Abstract：Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The Spike protein that mediates coronavirus entry into host cells is a major target for COVID-19 vaccines and antibody therapeutics. However, multiple variants of SARS-CoV-2 have emerged, which may potentially compromise vaccine effectiveness. Using a pseudovirus-based assay, we evaluated SARS-CoV-2 cell entry mediated by the viral Spike B.1.617 and B.1.1.7 variants. We also compared the neutralization ability of monoclonal antibodies from convalescent sera and neutralizing antibodies (NAbs) elicited by CoronaVac (inactivated vaccine) and ZF2001 (RBD-subunit vaccine) against B.1.617 and B.1.1.7 variants. Our results showed that, compared to D614G and B.1.1.7 variants, B.1.617 shows enhanced viral entry and membrane fusion, as well as more resistant to antibody neutralization. These findings have important implications for understanding viral infectivity and for immunization policy against SARS-CoV-2 variants.
由中国医学科学院流行病学微生物学研究所领导的研究团队在著名《新英格兰医学杂志》上发表通讯文章“Susceptibility of Circulating SARS-CoV-2 Variants to Neutralization”，研究了接种国药集团BBIBP-CorV灭活疫苗(Sinopharm)和北京科兴中维生物CoronaVac灭活疫苗(Sinovac)的志愿者血清，对新近出现的新冠突变毒株(主要是英国变异(B.1.1.7)和南非变异(B.1.1.351)毒株)的中和活性。https://www.nejm.org/doi/pdf/10.1056/NEJMc2103022
该研究选取了一组34名感染新冠后5个月的康复志愿者，第二组再选取25名接种两剂国药灭活疫苗，以及25名接种两剂科兴灭活疫苗后2-3周的健康志愿者。然后抽取志愿者血液分离血清。该研究第一个实验检测了新冠康复者血清和灭活疫苗接种者血清对野生型新冠假病毒毒株(即最开始武汉发现的毒株)中和活性，该结果发现疫苗接种志愿者的血清的中和活性与新冠感染康复者血清类似，并且略微低一些。由于新冠康复者的血清是5个月以后的样本，而疫苗接种者的血清是在接种后2-3周的样本，该时间点是抗体达到最高滴度的时期。因此，从这个结果可以得出两种灭活疫苗双剂接种后只诱导了低水平的体液免疫应答，既产生了低滴度的抗体 (图一)。
此外，新冠康复者中有4个样本没有检测到中和效价。6个国药BBIBP-CorV接种者样本中没有检测到中和效价(6/25)，4个科兴CoronaVac接种者样本中没有检测到中和效价(4/25)。https://www.nejm.org/doi/full/10.1056/NEJMc2103022
June 17, 2021
N Engl J Med 2021; 384:2354-2356
DOI: 10.1056/NEJMc2103022
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