COVID-19 患者在突破感染 SARS-CoV-2 变异株 Delta、Omicron-BA.1 和 Omicron-BA.5 期间的免疫反应。
Immune responses in COVID-19 patients during breakthrough infection with SARS-CoV-2 variants Delta, Omicron-BA.1 and Omicron-BA.5.
机构信息
Department of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
出版信息
Front Immunol. 2023 Jul 13;14:1150667. doi: 10.3389/fimmu.2023.1150667. eCollection 2023.
BACKGROUND
Breakthrough infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are increasingly observed in vaccinated individuals. Immune responses towards SARS-CoV-2 variants, particularly Omicron-BA.5, are poorly understood. We investigated the humoral and cellular immune responses of hospitalized COVID-19 patients during Delta and Omicron infection waves.
METHODS
The corresponding SARS-CoV-2 variant of the respective patients were identified by whole genome sequencing. Humoral immune responses were analyzed by ELISA and a cell culture-based neutralization assay against SARS-CoV-2 D614G isolate (wildtype), Alpha, Delta (AY.43) and Omicron (BA.1 and BA.5). Cellular immunity was evaluated with an IFN-γ ELISpot assay.
RESULTS
On a cellular level, patients showed a minor IFN-γ response after stimulating PBMCs with mutated regions of SARS-CoV-2 variants. Neutralizing antibody titers against Omicron-BA.1 and especially BA.5 were strongly reduced. Double-vaccinated patients with Delta breakthrough infection showed a significantly increased neutralizing antibody response against Delta compared to double-vaccinated uninfected controls (median complete neutralization titer (NT) 640 versus 80, p<0.05). Omicron-BA.1 infection increased neutralization titers against BA.1 in double-vaccinated patients (median NT of 160 in patients versus 20 in controls, p=0.07) and patients that received booster vaccination (median NT of 50 in patients versus 20 in controls, p=0.68). For boosted patients with BA.5 breakthrough infection, we found no enhancing effect on humoral immunity against SARS-CoV-2 variants.
CONCLUSION
Neutralizing antibody titers against Omicron-BA.1 and especially BA.5 were strongly reduced in SARS-CoV-2 breakthrough infections. Delta and Omicron-BA.1 but not Omicron-BA.5 infections boosted the humoral immunity in double-vaccinated patients and patients with booster vaccination. Despite BA.5 breakthrough infection, those patients may still be vulnerable for reinfections with BA.5 or other newly emerging variants of concern.
背景
突破性感染严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 变体在接种疫苗的个体中越来越常见。对 SARS-CoV-2 变体的免疫反应，特别是对奥密克戎 BA.5 的免疫反应，知之甚少。我们研究了 COVID-19 住院患者在德尔塔和奥密克戎感染浪潮期间对 SARS-CoV-2 变体的体液和细胞免疫反应。
方法
通过全基因组测序确定相应患者的 SARS-CoV-2 变体。通过 ELISA 分析和针对 SARS-CoV-2 D614G 分离株（野生型）、Alpha、Delta（AY.43）和奥密克戎（BA.1 和 BA.5）的细胞培养中和测定分析体液免疫反应。细胞免疫通过 IFN-γ ELISpot 测定进行评估。
结果
在细胞水平上，患者在用 SARS-CoV-2 变体的突变区域刺激 PBMC 后表现出轻微的 IFN-γ 反应。针对奥密克戎 BA.1 的中和抗体滴度尤其明显降低。突破性感染德尔塔的双疫苗接种患者与双疫苗接种未感染对照相比，针对 Delta 的中和抗体反应显著增加（中位数完全中和滴度（NT）640 对 80，p<0.05）。奥密克戎 BA.1 感染增加了双疫苗接种患者针对 BA.1 的中和抗体滴度（患者的中位数 NT 为 160，对照为 20，p=0.07）和接受加强接种的患者（患者的中位数 NT 为 50，对照为 20，p=0.68）。对于 BA.5 突破性感染的加强接种患者，我们没有发现针对 SARS-CoV-2 变体的体液免疫增强作用。
结论
针对奥密克戎 BA.1 的中和抗体滴度，尤其是 BA.5 的中和抗体滴度，在 SARS-CoV-2 突破性感染中明显降低。德尔塔和奥密克戎 BA.1 但不是奥密克戎 BA.5 感染增强了双疫苗接种患者和加强接种患者的体液免疫。尽管发生了 BA.5 突破性感染，但这些患者仍可能容易受到 BA.5 或其他新出现的关注变体的再感染。
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