The elicited anti-SARS-CoV-2 immunity is becoming increasingly complex with individuals receiving a different number of vaccine doses paired with or without recovery from breakthrough infections with different variants. Here we analyze the immunity of individuals that initially received two doses of mRNA vaccine and either received a booster vaccination, recovered from a breakthrough infection, or both. Our data suggest that two vaccine doses and delta breakthrough infection or three vaccine doses and optionally omicron or delta infection provide better B cell immunity than the initial two doses of mRNA vaccine with or without alpha breakthrough infection. A particularly potent B cell response against the currently circulating omicron variant (B. 1.1.529) was observed for thrice vaccinated individuals with omicron breakthrough infection; a 46-fold increase in plasma neutralization compared to two vaccine doses (p < 0.0001). The T cell response after two vaccine doses is not significantly influenced by additional antigen exposures. Of note, individuals with hybrid immunity show better correlated adaptive immune responses compared to those only vaccinated. Taken together, our data provide a detailed insight into SARS-CoV-2 immunity following different antigen exposure scenarios.

引发的抗 SARS-CoV-2 免疫力变得越来越复杂，因为个体接受了不同剂量的疫苗剂量，并且有或没有从不同变异体的突破性感染中恢复。在这里，我们分析了最初接受两剂 mRNA 疫苗并接受加强疫苗接种、从突破性感染中恢复或两者都接受的个体的免疫力。我们的数据表明，与有或没有 α 突破感染的最初两剂 mRNA 疫苗相比，两剂疫苗和 delta 突破感染或三剂疫苗和可选的 omicron 或 delta 感染提供更好的 B 细胞免疫。对于接种三次 omicron 突破性感染的个体，观察到针对当前循环的 omicron 变体（B.1.1.529）的特别有效的 B 细胞反应；p  < 0.0001）。两次疫苗剂量后的 T 细胞反应不受额外抗原暴露的显着影响。值得注意的是，与仅接种疫苗的个体相比，具有混合免疫的个体表现出更好的相关适应性免疫反应。总而言之，我们的数据提供了对不同抗原暴露情况下 SARS-CoV-2 免疫力的详细了解。