Reduced neutralisation of the Delta (B.1.617.2) SARS-CoV-2 variant of concern following vaccination.
Reduced neutralisation of the Delta (B.1.617.2) SARS-CoV-2 variant of concern following vaccination.
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DOI：
10.1371/journal.ppat.1010022
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发表时间：
2021-12
期刊：
影响因子：
6.7
通讯作者：
COVID-19 DeplOyed VaccinE (DOVE) Cohort Study investigators
中科院分区：
文献类型：
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作者：
Davis C;Logan N;Tyson G;Orton R;Harvey WT;Perkins JS;Mollett G;Blacow RM;COVID-19 Genomics UK (COG-UK) Consortium;Peacock TP;Barclay WS;Cherepanov P;Palmarini M;Murcia PR;Patel AH;Robertson DL;Haughney J;Thomson EC;Willett BJ;COVID-19 DeplOyed VaccinE (DOVE) Cohort Study investigators
疫苗被证明在控制与SARS-CoV-2感染相关的住院和死亡方面非常有效，但具有新抗原谱的病毒变体的出现可能会降低其效力。对疫苗接种者血清中和SARS-CoV-2变异体的能力进行评估，将为最大限度减少COVID-19病例和设计有效抗原制剂的策略的成功提供信息。在这里，我们检查了代表SARS-CoV-2谱系的B.1.617.1和B.1.617.2（首次与印度感染相关）和B.1.351（首次与南非感染相关）的令人担忧的变体（VOC）对接种BNT 162 b2（辉瑞/BioNTech）和ChAdOx 1（牛津/阿斯利康）疫苗的个体血清中和的敏感性。在所有接种疫苗的个体中，来自B.1.617.1和B.1.617.2的刺突糖蛋白分别使中和作用降低4.31和5.11倍。在B.1.617.2谱系中观察到的减少接近来自B.1.351（南非）变体的糖蛋白（6.29倍减少）所赋予的减少，已知其与疫苗效力降低相关。通过接种两个剂量的BNT 162 b2引起的中和抗体滴度显著高于通过接种两个剂量的ChAdOx 1引起的中和抗体滴度。BNT 162 b2两次给药后，中和滴度的幅度成倍降低，使B.1.617.1、B.1.617.2和B.1.351假病毒的滴度分别降低7.77、11.30和9.56倍，δ变体B.1.617.2的中和降低超过B.1.351。用两个剂量的ChAdOx 1接种的那些的倍数变化分别为0.69、4.01和1.48。这些VOC和其他VOC中突变的积累证明了抗原漂移和随后疫苗效力降低的可量化风险。因此，随着时间的推移，可能需要基于更新的变体的加强疫苗来预防生产性感染。该研究还表明，需要两种剂量方案的疫苗以获得最大的BNT 162 b2和ChAdOx 1诱导的免疫力。SARS-CoV-2病毒很可能是在2019年底中国武汉从蝙蝠到人类的跨物种跳跃之后出现的。随着病毒进化以适应人类，出现了新的病毒变体，这些变体在“刺突”基因中包含突变。刺突蛋白在病毒表面表达，它有助于进入人体细胞，是中和抗体的主要靶点。突变会改变刺突蛋白的形状，阻止抗体识别，使病毒能够逃避疫苗接种诱导的免疫力。使用从接种疫苗的人群中收集的样本作为COVID-19部署疫苗队列研究（DOVE）的一部分，我们评估了不同变体（β，κ和δ）逃避Astra Zeneca ChAdOx 1和Pfizer BNT 162 b2疫苗接种者保护性免疫反应的能力，这两种疫苗都是基于早期武汉病毒刺突基因。我们注意到来自两种疫苗接种者的疫苗血清对β和δ变体的中和作用降低。虽然疫苗在预防严重感染和死亡方面仍然非常有效，但由于病毒继续随着时间的推移而演变，特别是在弱势群体中，因此需要不断监测疫苗的有效性。
Vaccines are proving to be highly effective in controlling hospitalisation and deaths associated with SARS-CoV-2 infection but the emergence of viral variants with novel antigenic profiles threatens to diminish their efficacy. Assessment of the ability of sera from vaccine recipients to neutralise SARS-CoV-2 variants will inform the success of strategies for minimising COVID19 cases and the design of effective antigenic formulations. Here, we examine the sensitivity of variants of concern (VOCs) representative of the B.1.617.1 and B.1.617.2 (first associated with infections in India) and B.1.351 (first associated with infection in South Africa) lineages of SARS-CoV-2 to neutralisation by sera from individuals vaccinated with the BNT162b2 (Pfizer/BioNTech) and ChAdOx1 (Oxford/AstraZeneca) vaccines. Across all vaccinated individuals, the spike glycoproteins from B.1.617.1 and B.1.617.2 conferred reductions in neutralisation of 4.31 and 5.11-fold respectively. The reduction seen with the B.1.617.2 lineage approached that conferred by the glycoprotein from B.1.351 (South African) variant (6.29-fold reduction) that is known to be associated with reduced vaccine efficacy. Neutralising antibody titres elicited by vaccination with two doses of BNT162b2 were significantly higher than those elicited by vaccination with two doses of ChAdOx1. Fold decreases in the magnitude of neutralisation titre following two doses of BNT162b2, conferred reductions in titre of 7.77, 11.30 and 9.56-fold respectively to B.1.617.1, B.1.617.2 and B.1.351 pseudoviruses, the reduction in neutralisation of the delta variant B.1.617.2 surpassing that of B.1.351. Fold changes in those vaccinated with two doses of ChAdOx1 were 0.69, 4.01 and 1.48 respectively. The accumulation of mutations in these VOCs, and others, demonstrate the quantifiable risk of antigenic drift and subsequent reduction in vaccine efficacy. Accordingly, booster vaccines based on updated variants are likely to be required over time to prevent productive infection. This study also suggests that two dose regimes of vaccine are required for maximal BNT162b2 and ChAdOx1-induced immunity. The SARS-CoV-2 virus is likely to have emerged following a cross-species jump from bats to humans in Wuhan, China at the end of 2019. As the virus has evolved to adapt to humans, new viral variants have emerged that incorporate mutations in the “spike” gene. The spike protein is expressed on the surface of the virus, it facilitates entry into human cells and is the main target of neutralising antibodies. Mutations change the shape of the spike protein, preventing antibody recognition and enabling the virus to escape from the immunity induced by vaccination. Using samples collected from vaccinated people as part of the COVID-19 Deployed Vaccine Cohort Study (DOVE), we assessed the capacity of different variants (beta, kappa and delta) to evade the protective immune response in recipients of the Astra Zeneca ChAdOx1 and Pfizer BNT162b2 vaccines, both of which are based on the early Wuhan virus spike gene. We noted a reduction in neutralisation of both the beta and delta variants by vaccine sera from recipients of both vaccines. While vaccines remain highly effective at preventing severe infection and death, ongoing monitoring of vaccine effectiveness is indicated as the virus continues to evolve over time, especially in vulnerable groups.