对 SARS-CoV-2 恢复期患者队列的分析表明，β和奥密克戎变异株通过共同策略逃避了疫苗诱导的针对 RBD 的抗体。

Analysis of a SARS-CoV-2 convalescent cohort identified a common strategy for escape of vaccine-induced anti-RBD antibodies by Beta and Omicron variants.

机构信息

Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, United States.

Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, United States; Department of Medicine, Harvard Medical School, Boston, MA, United States.

出版信息

EBioMedicine. 2022 Jun;80:104025. doi: 10.1016/j.ebiom.2022.104025. Epub 2022 May 6.

DOI:10.1016/j.ebiom.2022.104025

PMID:35533497

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9073271/

Abstract

BACKGROUND

Evolutionary pressure has led to the emergence of SARS-CoV-2 variants, with the most recent Omicron variant containing an unparalleled 30 mutations in the spike protein. Many of these mutations are expected to increase immune evasion, thus making breakthrough cases and re-infection more common.

METHODS

From June 2020 to December 2021 serial blood samples (initial post recovery, 6 months, 12 months) were collected from a COVID-19 convalescent cohort in Boston, MA. Plasma was isolated for use in Mesoscale Discovery based antibody binding assays. Unvaccinated donors or those vaccinated prior to the primary blood draw were excluded from this analysis, as were those who did not have at least two blood draws. Wilcoxon signed rank tests were used to compare pre- and post-vaccination titers and antibody response against different variants, while McNemar tests were used to compare the proportions of achieving ≥ 4 fold increases against different variants.

FINDINGS

Forty-eight COVID convalescent donors with post-infection vaccination (hybrid immunity) were studied to evaluate the levels of cross-reactive antibodies pre- and post- vaccination against various SARS-CoV-2 Spike and receptor binding domain (RBD) proteins. Vaccination with BNT162b2, mRNA-1273 or Ad26.COV2.S led to a 6·3 to 7·8 fold increase in anti-Spike antibody titers and a 7·0 to 7·4 fold increase in anti-WT, Alpha and Delta RBD antibody. However, a lower response was observed for Beta and Omicron RBDs with only 7/48 (15%) and 15/48 (31%) donors having a ≥4 fold increase in post-vaccination titers against Beta and Omicron RBDs. Structural analysis of the Beta and Omicron RBDs reveal a shared immune escape strategy involving residues K417-E484-N501 that is exploited by these variants of concern.

INTERPRETATION

Through mutations of the K417-E484-N501 triad, SARS-CoV-2 has evolved to evade neutralization by the class I/II anti-RBD antibody fraction of hybrid immunity plasma as the polyclonal antibody response post-vaccination shows limitations in the ability to solve the structural requirements to bind the mutant RBDs.

FUNDING

Massachusetts Consortium on Pathogen Readiness (280870.5116709.0016) and the National Institute of Allergy and Infectious Diseases (1R01AI161152-01A1).

摘要

背景

进化压力导致了 SARS-CoV-2 变体的出现，最近的奥密克戎变体在刺突蛋白中包含了无与伦比的 30 个突变。这些突变预计会增加免疫逃逸，从而使突破性感染和再感染更为常见。

方法

从 2020 年 6 月至 2021 年 12 月，从马萨诸塞州波士顿的 COVID-19 康复队列中连续采集血清样本（康复后初期、6 个月、12 个月）。分离血浆用于基于 Mesoscale Discovery 的抗体结合测定。未接种疫苗的供体或在首次采血前接种疫苗的供体，以及至少未采集两次血样的供体，均不纳入本分析。采用 Wilcoxon 符号秩检验比较疫苗接种前后的滴度和针对不同变体的抗体反应，采用 McNemar 检验比较针对不同变体达到 ≥4 倍增长的比例。

结果

研究了 48 名 COVID 康复供体的混合免疫后感染疫苗接种情况，以评估接种前后针对各种 SARS-CoV-2 刺突和受体结合域（RBD）蛋白的交叉反应性抗体水平。接种 BNT162b2、mRNA-1273 或 Ad26.COV2.S 后，抗刺突抗体滴度增加了 6.3 至 7.8 倍，抗 WT、Alpha 和 Delta RBD 抗体增加了 7.0 至 7.4 倍。然而，Beta 和 Omicron RBD 的反应较低，只有 48 名供体中的 7/48（15%）和 15/48（31%）在 Beta 和 Omicron RBD 疫苗接种后滴度增加≥4 倍。对 Beta 和 Omicron RBD 的结构分析表明，这些变体都存在一个共同的免疫逃逸策略，涉及 K417-E484-N501 三联体的突变，从而逃避了混合免疫血浆中 I/II 类抗 RBD 抗体的中和作用。