Neutralisation of SARS-CoV-2 lineage P.1 by antibodies elicited through natural SARS-CoV-2 infection or vaccination with an inactivated SARS-CoV-2 vaccine: an immunological study.-猫眼课题宝

DOI：

10.1016/s2666-5247(21)00129-4

发表时间：

2021-10

期刊：

The Lancet. Microbe

影响因子：

通讯作者：

中科院分区：

其他

文献类型：

作者：

Souza WM;Amorim MR;Sesti-Costa R;Coimbra LD;Brunetti NS;Toledo-Teixeira DA;de Souza GF;Muraro SP;Parise PL;Barbosa PP;Bispo-Dos-Santos K;Mofatto LS;Simeoni CL;Claro IM;Duarte ASS;Coletti TM;Zangirolami AB;Costa-Lima C;Gomes ABSP;Buscaratti LI;Sales FC;Costa VA;Franco LAM;Candido DS;Pybus OG;de Jesus JG;Silva CAM;Ramundo MS;Ferreira GM;Pinho MC;Souza LM;Rocha EC;Andrade PS;Crispim MAE;Maktura GC;Manuli ER;Santos MNN;Camilo CC;Angerami RN;Moretti ML;Spilki FR;Arns CW;Addas-Carvalho M;Benites BD;Vinolo MAR;Mori MAS;Gaburo N;Dye C;Marques-Souza H;Marques RE;Farias AS;Diamond MS;Faria NR;Sabino EC;Granja F;Proença-Módena JL

来源链接：

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266272/

SARS-CoV-2谱系P.1产生的突变-于2021年1月初在巴西首次发现-包括病毒刺突蛋白受体结合结构域的氨基酸变化，这些变化也在其他令人担忧的变体中报道，包括B.1.1.7和B.1.351。我们的目的是调查野生型P.1谱系SARS-CoV-2的分离株是否可以逃避多克隆免疫反应产生的中和抗体。我们进行了一项免疫学研究，以评估抗体对SARS-CoV-2的谱系P.1和谱系B分离株的中和作用，使用来自先前感染SARS-CoV-2或接种SARS-CoV-2疫苗的患者的血浆样本。从巴西马瑙斯患者采集的鼻咽和支气管肺泡灌洗样本中获得了两份含有SARS-CoV-2谱系P.1（经病毒基因组测序证实）的标本（P.1/28和P.1/30），并与2020年2月从巴西一名患者中回收的SARS-CoV-2谱系B分离株（SARS.CoV2/SP02.2020）进行了比较。将分离株与来自21名先前患有COVID-19的献血者和总共53名化学灭活SARS-CoV-2疫苗CoronaVac接受者的血浆样本一起孵育：18名接受单剂量后的个体和另外20名个体（共38例）接受两剂后（最近一次给药后17-38天采集）;以及15名在疫苗3期试验期间接受两剂疫苗的个体（在第二剂疫苗后134-230天收集）。根据中位病毒中和滴度（VNT 50，定义为显示对细胞病变效应的50%保护的样品稀释度的倒数值），比较血浆样本对P.1/28、P.1/30和B分离株的抗体中和。就VNT 50而言，来自先前感染SARS-CoV-2的个体的血浆对P.1分离株的中和能力低8.6倍（P.1/28的中值VNT 50为30 [IQR <20-45]，P.1/30的中值VNT 50为30 [<20-40]）（260 [160-400]），二项式模型显示与谱系B分离株相比，谱系P.1分离株显著降低（p≤0·0001）。从20-23天前接种第一剂CoronaVac的个体中采集的血浆样本未观察到P.1分离株的有效中和作用（大多数血浆样品的VNT 50低于检测限[<20]），提前17-38天进行第二次给药（P.1/28的中位VNT 50为24 [IQR <20 - 25]，P.1/30的中位VNT 50为28 [<20-25]），或提前134-260天进行第二次给药（所有VNT 50均低于检测限）。在20-23天前首次给予CoronaVac后，抗谱系B分离株的中位VNT 50为20（IQR 20-30），在17-38天前第二次给药后为75（<20-263），在134-260天前第二次给药后为20（<20-30）。在CoronaVac第二次给药后17-38天采集的血浆中，与对谱系B分离株的中和能力相比，对两种P.1分离株的中和能力显著降低（P.1/28的p= 0.0051，P.1/30的p= 0.0336）。所有数据都得到了通过菌斑减少中和试验获得的结果的证实。SARS-CoV-2谱系P.1可能逃脱由针对先前传播的SARS-CoV-2变体的多克隆刺激产生的抗体的中和。对SARS-CoV-2的持续基因组监测结合抗体中和试验可以帮助指导国家免疫规划。圣保罗研究基金会、巴西科学、技术和创新部和研究供资局、医学研究理事会、国家科学和技术发展理事会、国家卫生研究院。摘要的葡萄牙语翻译见补充材料部分。

Mutations accrued by SARS-CoV-2 lineage P.1—first detected in Brazil in early January, 2021—include amino acid changes in the receptor-binding domain of the viral spike protein that also are reported in other variants of concern, including B.1.1.7 and B.1.351. We aimed to investigate whether isolates of wild-type P.1 lineage SARS-CoV-2 can escape from neutralising antibodies generated by a polyclonal immune response. We did an immunological study to assess the neutralising effects of antibodies on lineage P.1 and lineage B isolates of SARS-CoV-2, using plasma samples from patients previously infected with or vaccinated against SARS-CoV-2. Two specimens (P.1/28 and P.1/30) containing SARS-CoV-2 lineage P.1 (as confirmed by viral genome sequencing) were obtained from nasopharyngeal and bronchoalveolar lavage samples collected from patients in Manaus, Brazil, and compared against an isolate of SARS-CoV-2 lineage B (SARS.CoV2/SP02.2020) recovered from a patient in Brazil in February, 2020. Isolates were incubated with plasma samples from 21 blood donors who had previously had COVID-19 and from a total of 53 recipients of the chemically inactivated SARS-CoV-2 vaccine CoronaVac: 18 individuals after receipt of a single dose and an additional 20 individuals (38 in total) after receipt of two doses (collected 17–38 days after the most recent dose); and 15 individuals who received two doses during the phase 3 trial of the vaccine (collected 134–230 days after the second dose). Antibody neutralisation of P.1/28, P.1/30, and B isolates by plasma samples were compared in terms of median virus neutralisation titre (VNT50, defined as the reciprocal value of the sample dilution that showed 50% protection against cytopathic effects). In terms of VNT50, plasma from individuals previously infected with SARS-CoV-2 had an 8·6 times lower neutralising capacity against the P.1 isolates (median VNT50 30 [IQR <20–45] for P.1/28 and 30 [<20–40] for P.1/30) than against the lineage B isolate (260 [160–400]), with a binominal model showing significant reductions in lineage P.1 isolates compared with the lineage B isolate (p≤0·0001). Efficient neutralisation of P.1 isolates was not seen with plasma samples collected from individuals vaccinated with a first dose of CoronaVac 20–23 days earlier (VNT50s below the limit of detection [<20] for most plasma samples), a second dose 17–38 days earlier (median VNT50 24 [IQR <20–25] for P.1/28 and 28 [<20–25] for P.1/30), or a second dose 134–260 days earlier (all VNT50s below limit of detection). Median VNT50s against the lineage B isolate were 20 (IQR 20–30) after a first dose of CoronaVac 20–23 days earlier, 75 (<20–263) after a second dose 17–38 days earlier, and 20 (<20–30) after a second dose 134–260 days earlier. In plasma collected 17–38 days after a second dose of CoronaVac, neutralising capacity against both P.1 isolates was significantly decreased (p=0·0051 for P.1/28 and p=0·0336 for P.1/30) compared with that against the lineage B isolate. All data were corroborated by results obtained through plaque reduction neutralisation tests. SARS-CoV-2 lineage P.1 might escape neutralisation by antibodies generated in response to polyclonal stimulation against previously circulating variants of SARS-CoV-2. Continuous genomic surveillance of SARS-CoV-2 combined with antibody neutralisation assays could help to guide national immunisation programmes. São Paulo Research Foundation, Brazilian Ministry of Science, Technology and Innovation and Funding Authority for Studies, Medical Research Council, National Council for Scientific and Technological Development, National Institutes of Health. For the Portuguese translation of the abstract see Supplementary Materials section.

Neutralisation of SARS-CoV-2 lineage P.1 by antibodies elicited through natural SARS-CoV-2 infection or vaccination with an inactivated SARS-CoV-2 vaccine: an immunological study.

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