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接种 BNT162b2 疫苗的老年人对 21 种 SARS-CoV-2 变异体的中和抗体活性。

Neutralizing antibody activity against 21 SARS-CoV-2 variants in older adults vaccinated with BNT162b2.

机构信息

The Pirbright Institute, Guildford, UK.

Nuffield Department of Medicine, The Jenner Institute, Oxford, UK.

出版信息

Nat Microbiol. 2022 Aug;7(8):1180-1188. doi: 10.1038/s41564-022-01163-3. Epub 2022 Jul 14.

DOI:10.1038/s41564-022-01163-3
PMID:35836002
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9352594/
Abstract

SARS-CoV-2 variants may threaten the effectiveness of vaccines and antivirals to mitigate serious COVID-19 disease. This is of most concern in clinically vulnerable groups such as older adults. We analysed 72 sera samples from 37 individuals, aged 70-89 years, vaccinated with two doses of BNT162b2 (Pfizer-BioNTech) 3 weeks apart, for neutralizing antibody responses to wildtype SARS-CoV-2. Between 3 and 20 weeks after the second vaccine dose, neutralizing antibody titres fell 4.9-fold to a median titre of 21.3 (neutralization dose 80%), with 21.6% of individuals having no detectable neutralizing antibodies at the later time point. Next, we examined neutralization of 21 distinct SARS-CoV-2 variant spike proteins with these sera, and confirmed substantial antigenic escape, especially for the Omicron (B.1.1.529, BA.1/BA.2), Beta (B.1.351), Delta (B.1.617.2), Theta (P.3), C.1.2 and B.1.638 spike variants. By combining pseudotype neutralization with specific receptor-binding domain (RBD) enzyme-linked immunosorbent assays, we showed that changes to position 484 in the spike RBD were mainly responsible for SARS-CoV-2 neutralizing antibody escape. Nineteen sera from the same individuals boosted with a third dose of BNT162b2 contained higher neutralizing antibody titres, providing cross-protection against Omicron BA.1 and BA.2. Despite SARS-CoV-2 immunity waning over time in older adults, booster vaccines can elicit broad neutralizing antibodies against a large number of SARS-CoV-2 variants in this clinically vulnerable cohort.

摘要

SARS-CoV-2 变体可能会威胁到疫苗和抗病毒药物减轻严重 COVID-19 疾病的效果。这在临床脆弱群体中最为令人担忧，如老年人。我们分析了 37 名年龄在 70-89 岁的个体的 72 份血清样本，这些个体在相隔 3 周的时间内接受了两剂 BNT162b2（辉瑞-生物科技）疫苗接种，以针对野生型 SARS-CoV-2 产生中和抗体反应。在第二剂疫苗接种后 3 至 20 周，中和抗体滴度下降 4.9 倍，中位数滴度为 21.3（中和剂量 80%），21.6%的个体在较晚时间点没有检测到中和抗体。接下来，我们用这些血清检测了 21 种不同的 SARS-CoV-2 变体刺突蛋白的中和作用，并证实了明显的抗原逃逸，特别是对奥密克戎（B.1.1.529，BA.1/BA.2）、贝塔（B.1.351）、德尔塔（B.1.617.2）、西塔（P.3）、C.1.2 和 B.1.638 刺突变体。通过将假型中和与特定的受体结合域（RBD）酶联免疫吸附试验相结合，我们表明，刺突 RBD 中位置 484 的变化主要导致了 SARS-CoV-2 中和抗体的逃逸。来自同一个体的 19 份血清在接受第三剂 BNT162b2 后含有更高的中和抗体滴度，对奥密克戎 BA.1 和 BA.2 提供了交叉保护。尽管老年人的 SARS-CoV-2 免疫力随时间减弱，但加强疫苗可以在这个临床脆弱群体中引发针对大量 SARS-CoV-2 变体的广泛中和抗体。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7a9/9352594/b867b2fe71db/41564_2022_1163_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7a9/9352594/b3174b2b8428/41564_2022_1163_Fig5_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7a9/9352594/e7b332f6c8e4/41564_2022_1163_Fig6_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7a9/9352594/78f224c37f46/41564_2022_1163_Fig7_ESM.jpg
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