Biomedical Pioneering Innovation Center (BIOPIC), School of Life Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing, People's Republic of China.
Changping Laboratory, Beijing, People's Republic of China.
Emerg Microbes Infect. 2024 Dec;13(1):2412623. doi: 10.1080/22221751.2024.2412623. Epub 2024 Oct 15.
SARS-CoV-2 ancestral strain-induced immune imprinting poses great challenges to updating vaccines for new variants. Studies showed that repeated Omicron exposures could override immune imprinting induced by inactivated vaccines but not mRNA vaccines, a disparity yet to be understood. Here, we analyzed the immune imprinting alleviation in inactivated vaccine (CoronaVac) cohorts after a long-term period following breakthrough infections (BTI). We observed in CoronaVac-vaccinated individuals who experienced BA.5/BF.7 BTI, the proportion of Omicron-specific memory B cells (MBCs) substantially increased after an extended period post-Omicron BTI, with their antibodies displaying enhanced somatic hypermutation and neutralizing potency. Consequently, the neutralizing antibody epitope distribution encoded by MBCs post-BA.5/BF.7 BTI after prolonged maturation closely mirrors that in BA.5/BF.7-infected unvaccinated individuals. Together, these results indicate the activation and expansion of Omicron-specific naïve B cells generated by first-time Omicron exposure helped to alleviate CoronaVac-induced immune imprinting, and the absence of this process should have caused the persistent immune imprinting seen in mRNA vaccine recipients.
SARS-CoV-2 原始株诱导的免疫印迹对更新针对新变体的疫苗构成了巨大挑战。研究表明，重复的奥密克戎暴露可以克服灭活疫苗诱导的免疫印迹，但不能克服 mRNA 疫苗诱导的免疫印迹，这种差异尚待理解。在这里，我们分析了突破性感染（BTI）后长期接种灭活疫苗（科兴疫苗）的人群中的免疫印迹缓解情况。我们观察到，在接种科兴疫苗的个体中，经历了 BA.5/BF.7 BTI 后，奥密克戎特异性记忆 B 细胞（MBC）的比例在奥密克戎 BTI 后很长一段时间内显著增加，其抗体显示出增强的体细胞超突变和中和效力。因此，在 BA.5/BF.7 感染未接种疫苗的个体中，MBC 编码的中和抗体表位分布在 BA.5/BF.7 BTI 后延长成熟后与 BA.5/BF.7 感染后非常相似。总之，这些结果表明，首次奥密克戎暴露产生的奥密克戎特异性幼稚 B 细胞的激活和扩增有助于缓解科兴疫苗诱导的免疫印迹，而 mRNA 疫苗受种者中持续存在的免疫印迹可能是由于缺乏这一过程。
