National Health Commission Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China.
Haihe Laboratory of Cell Ecosystem, Tianjin, People's Republic of China.
Emerg Microbes Infect. 2023 Dec;12(1):2202263. doi: 10.1080/22221751.2023.2202263.
The adaptive immunity against SARS-CoV-2 prototype strain and Omicron sublineages induced by BA.1 breakthrough infection in vaccinees of inactivated COVID-19 vaccines have not been well characterized. Here, we report that BA.1 breakthrough infection induced mucosal sIgA and resulted in higher IgG titers against prototype strain and Omicron sublineages in vaccinees than in vaccine naïve-infected individuals. BA.1 breakthrough infection boosted antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis to prototype strain and BA.1, BA.1.1, BA.2, BA.2.12.1, and BA.2.75 but not BA.4/5 and induced neutralization against prototype strain and BA.1, BA.1.1, BA.2, BA.2.12.1, BA.2.75, and BA.4/5 but not BF.7, BQ.1, and XBB. In total, BA.1 breakthrough infection individuals produced less extensive sIgA, plasma IgG and NAb responses against Omicron sublineages compared with those against prototype strain. Further, BA.1 breakthrough infection induced recall B cell response to prototype strain and Omicron variant, primarily targeting memory B cells producing conserved epitopes. Memory T cell responses against Omicron is largely preserved. Individuals with vaccine booster did not induce more beneficial immune responses to Omicron sublineages upon BA.1 breakthrough infection than those with primary vaccine dose only. The breakthrough infection individuals produced stronger adaptive immunity than those of inactivated vaccine-healthy individuals. These data have important implications for understanding the vaccine effectiveness and adaptive immunity to breakthrough infection in individuals fully immunized with inactivated vaccines. Omicron sublineages, especially for those emerged after BA.4/5 strain, evade NAb responses induced by BA.1 breakthrough infection. It is urgent to optimize the vaccine immunogen design and formulations to SARS-CoV-2 variants.
BA.1 突破性感染诱导的灭活 COVID-19 疫苗接种者针对 SARS-CoV-2 原型株和奥密克戎亚谱系的适应性免疫尚未得到很好的描述。在这里，我们报告称，BA.1 突破性感染诱导了黏膜 sIgA，并导致疫苗接种者针对原型株和奥密克戎亚谱系的 IgG 滴度高于未接种疫苗的感染个体。BA.1 突破性感染增强了抗体依赖的细胞细胞毒性和抗体依赖的细胞吞噬作用，针对原型株和 BA.1、BA.1.1、BA.2、BA.2.12.1 和 BA.2.75，但不针对 BA.4/5，并诱导针对原型株和 BA.1、BA.1.1、BA.2、BA.2.12.1、BA.2.75 和 BA.4/5 的中和作用，但不针对 BF.7、BQ.1 和 XBB。总的来说，与针对原型株相比，BA.1 突破性感染个体产生的针对奥密克戎亚谱系的 sIgA、血浆 IgG 和 NAb 反应范围较小。此外，BA.1 突破性感染诱导了针对原型株和奥密克戎变体的记忆 B 细胞反应，主要针对产生保守表位的记忆 B 细胞。针对奥密克戎的记忆 T 细胞反应基本得到保留。与仅接受过初级疫苗剂量的个体相比，接受过疫苗加强剂的个体在 BA.1 突破性感染后针对奥密克戎亚谱系并未诱导出更有益的免疫反应。突破性感染个体产生的适应性免疫强于已完全接种灭活疫苗的健康个体。这些数据对于理解完全接种灭活疫苗的个体对突破性感染的疫苗有效性和适应性免疫具有重要意义。奥密克戎亚谱系，特别是在 BA.4/5 株之后出现的亚谱系，逃避了由 BA.1 突破性感染诱导的 NAb 反应。急需优化 SARS-CoV-2 变异疫苗免疫原设计和配方。
