拉姆达变异株简介

1、拉姆达变异株简介拉姆达变异株简介Lambda variant of SARS-CoV-214一、全球新冠病毒不同变异及分类汇一、全球新冠病毒不同变异及分类汇总总5不同变异新冠病毒株重视程度：不同变异新冠病毒株重视程度：VUI需要进一步观察株需要进一步观察株variant under investigationVOI有意义的变异株有意义的变异株variant of interestVOC值得关注变异株值得关注变异株variant of concernVOHC严重？严重？（高）后果的变异（高）后果的变异variant of high consequence6Variant of InterestA

2、 variant with specific genetic markers that have been associated with changes to：1. receptor binding,2. reduced neutralization by antibodies generated against previous infection or vaccination,3. reduced efficacy of treatments,4. potential diagnostic impact,5. or predicted increase in transmissibili

3、ty6. or disease severity.7Possible attributes of a variant of interest:Specific genetic markers that are predicted to affect transmission, diagnostics, therapeutics, or immune escape.Evidence that it is the cause of an increased proportion of cases or unique outbreak clusters.Limited prevalence or e

4、xpansion in the US or in other countries.A variant of interest might require one or more appropriate public health actions, including enhanced sequence surveillance, enhanced laboratory characterization, or epidemiological investigations to assess how easily the virus spreads to others, the severity

5、 of disease, the efficacy of therapeutics and whether currently authorized vaccines offer protection.8Variant of ConcernA variant for which there is evidence of：1. an increase in transmissibility,2. more severe disease (e.g., increased hospitalizations or deaths),3. significant reduction in neutrali

6、zation by antibodies generated during previous infection or vaccination,4. reduced effectiveness of treatments or vaccines,5. or diagnostic detection failures.9Possible attributes of a variant of concern:In addition to the possible attributes of a variant of interestEvidence of impact on diagnostics

7、, treatments, or vaccines1. Widespread interference with diagnostic test targets2. Evidence of substantially decreased susceptibility to one or more class of therapies3. Evidence of significant decreased neutralization by antibodies generated during previous infection or vaccination4. Evidence of re

8、duced vaccine-induced protection from severe disease Evidence of increased transmissibility Evidence of increased disease severity10Possible attributes of a variant of concern:Variants of concern might require one or more appropriate public health actions, such as notification to WHO under the Inter

9、national Health Regulations, reporting to CDC, local or regional efforts to control spread, increased testing, or research to determine the effectiveness of vaccines and treatments against the variant. Based on the characteristics of the variant, additional considerations may include the development

10、 of new diagnostics or the modification of vaccines or treatments.113、Variant of High ConsequenceA variant of high consequence has clear evidence that prevention measures ormedical countermeasures (MCMs) have significantly reduced effectiveness relative to previously circulating variants.Possible at

11、tributes of a variant of high consequence:In addition to the possible attributes of a variant of concernImpact on Medical Countermeasures (MCM)1. Demonstrated failure of diagnostic test targets2. Evidence to suggest a significantly reduction in vaccine effectiveness, adisproportionately high number

12、of vaccine breakthrough cases, or very low vaccine-induced protection against severe disease3. Significantly reduced susceptibility to multiple EUA or approved therapeutics4. More severe clinical disease and increased hospitalizations12Variant of High ConsequenceA variant of high consequence would r

13、equire notification to WHO under the International Health Regulations, reporting to CDC, an announcement of strategies to prevent or contain transmission, and recommendations to update treatments and vaccines.Currently, there are no SARS-CoV-2 variants that rise to the level of high consequence.EUA获

14、批的单克隆抗体的运获批的单克隆抗体的运用用：Lilly、REG、GSK!13三个单三个单抗抗EUA的适的适应应症症及及限制限制使使用相用相似似！1415最新的最新的VOC、VOI及其他变异病毒株汇总及其他变异病毒株汇总：15？Variants of concern (WHO)1. Alpha (lineage B.1.1.7)，B.1.1.7 with E484K2. Beta (lineage B.1.351)3. Gamma (lineage P.1)4. Delta (lineage B.1.617.2)Variants of interest (WHO)1. Eta (lineage

15、B.1.525)2. Iota (lineage B.1.526)3. Kappa (lineage B.1.617.1)4. Lambda (lineage C.37)16最新的最新的VOC、VOI及其他变异病毒株汇总及其他变异病毒株汇总：15？Former variants of interest1. Epsilon (lineages B.1.429, B.1.427, CAL.20C)2. Zeta (lineage P.2)3. Theta (lineage P.3)Other notable variants 1. R.12. Lineage B.1.1.2073. Lineage

16、 B.1.6204. Additional variants17二、拉姆达变异二、拉姆达变异株株Lambda variant特性简介特性简介18Lambda variant：又又名名 lineage C.37in December 2020首次发现于秘首次发现于秘鲁鲁 in Peru.On 14 June 2021, WHO命名为命名为Lambda变异株及变异株及VOI全球全球有有30至至少少30个国家个国家与其他变异株相比对于中和抗体的抵抗力更强：与其他变异株相比对于中和抗体的抵抗力更强：It is known to bemore resistant to neutralizing anti

17、bodies compared to other strains.研究提示传染性更高，对于疫苗的抵抗力更高研究提示传染性更高，对于疫苗的抵抗力更高于于Alpha和和Gamma：It is also suggested that the Lambda variant could be more infectious and resistant to vaccines than the Alpha and/or Gamma variant.19Lambda变异株变异株S区主要变异区主要变异:1. G75V2. T76I3. 246-2524. L452Q5. F490S6. D614G7. T85

18、9NLambda突突变变株株的的病病毒毒学和学和免免疫学疫学特特征征 RSYLTPGD246-253N、L452Q和和F490S突突 变，导致其免疫逃逸能力增强；变，导致其免疫逃逸能力增强； T76I和和L452Q突突变，导致其传染性增变，导致其传染性增强强。 RSYLTPGD246-253N突变与突变与N端结构域端结构域（NTD）“超超级级位位点点”的的一个一个组组成部分成部分重重叠，表明这是叠，表明这是其其免疫优势位免疫优势位点。点。因此因此，该该 位点位点的的突变突变使使Lambda突变株能够逃突变株能够逃逸逸新新 冠疫苗引发的免疫反应冠疫苗引发的免疫反应。 实际上，仅仅实际上，仅仅增增

19、加传染性并不加传染性并不能能导致导致大大规规 模感模感染染，Epsilon突变突变株株就就是是例例子子，该，该突突变变 株传染性更高，但免疫逃逸能力并未增强株传染性更高，但免疫逃逸能力并未增强， 因此并未导致大规模感染因此并未导致大规模感染。 要实现大规模要实现大规模感感染染，必须具备，必须具备两两个特个特征征： 传染性增加和传染性增加和免免疫逃逸能力增疫逃逸能力增加加，有，有研研究究 提提示示Lambda突变株具备这两种突变株具备这两种能能力力。 该研究通过分该研究通过分子子系统发育分析系统发育分析和和病毒病毒学学实实 验阐明了验阐明了Lambda突变株的进化突变株的进化趋势趋势。 尽尽管目

20、管目前前WHO仅仅将其归将其归类类为待为待观观察察突突变变 株（株（VOI），但但该该论论文文作者作者强强调调Lambda突变株具有很突变株具有很强强的潜力在未来的潜力在未来引引发新发新的的大大规模流规模流行，行，应当做好应对准应当做好应对准备备。2021病毒出现病毒出现的的 T76I 和和 L452Q 两个两个突突变变，这两个突这两个突变增变增强了该变强了该变种种与与ACE2 细细胞胞受受体结体结合合 的性的性质质，所以传染性增，所以传染性增高高。在最新研究在最新研究中中，日本东京大学和大阪大学研究人员日本东京大学和大阪大学研究人员称称，拉姆达变种拉姆达变种的的刺突蛋白具刺突蛋白具有有高高度

21、度 传染传染性性，而导致这种高传染性，而导致这种高传染性的的“罪魁祸首罪魁祸首”是该病毒出现是该病毒出现的的T76I和和L452Q两个两个突突变变， 这两个突变改变了该变种这两个突变改变了该变种与与ACE2细细胞胞受体结受体结合合的性质的性质。研究人员表研究人员表示示，尽管这项研究迄今尚未经过同行评，尽管这项研究迄今尚未经过同行评审审，但可以确定但可以确定拉拉姆达变种病姆达变种病毒毒感感染染 细胞的活跃程度不亚于德尔塔变细胞的活跃程度不亚于德尔塔变种种后者目前被认为是世界上最具传染性的毒株之后者目前被认为是世界上最具传染性的毒株之一一。研究还指研究还指出出，RSYLTPGD246-253N、L

22、452Q和和F490S突变让拉姆达变异毒株可以对抗免突变让拉姆达变异毒株可以对抗免 疫疫性性。其其中中，RSYLTPGD246-253N突变突变是是拉拉姆姆达达刺刺突突蛋蛋白白N端端结构结构域域中中一一种种独独特特的的7个个 氨基酸缺失突氨基酸缺失突变变，负责逃避中和抗负责逃避中和抗体体，专家将这种突变描述专家将这种突变描述为为“独独特特”的突的突变变只存只存 在于拉姆达变种病毒在于拉姆达变种病毒中中。拉拉美美社社近日报近日报道道，RSYLTPGD246-253N也也被称被称为为“安安第第斯突斯突变变”，为为了中了中和和具有具有这这种种 突变的病毒变突变的病毒变种种，大约需要产生比中和其他毒株

23、，大约需要产生比中和其他毒株多多1.5倍的抗体，这是因倍的抗体，这是因为为N端端结结构域构域的的 大部分基因编码区序列消失大部分基因编码区序列消失了了，而抗体，而抗体通通常在这个位常在这个位置置与可能进入与可能进入细细胞的刺突蛋胞的刺突蛋白白结结合合。Amino acid mutations of SARS-CoV-2 Lambda variant plotted on a genome map of SARS-CoV-2 with a focus on the spike2223First samples of the Lambda variant were detected inHisto

24、ryin December 2020 Peruby April 2021over eighty percent of new cases of COVID-19 inPeru were from the new variant.In mid-June 202190.6% of new COVID-19 cases in Arequipa and 78.1% of new cases in Cusco were the Lambda variant, according to the Peruvian Ministry of Health.By this time the Lambda variant had also spread