Goel Rishi R, Painter Mark M, Lundgreen Kendall A, Apostolidis Sokratis A, Baxter Amy E, Giles Josephine R, Mathew Divij, Pattekar Ajinkya, Reynaldi Arnold, Khoury David S, Gouma Sigrid, Hicks Philip, Dysinger Sarah, Hicks Amanda, Sharma Harsh, Herring Sarah, Korte Scott, Kc Wumesh, Oldridge Derek A, Erickson Rachel I, Weirick Madison E, McAllister Christopher M, Awofolaju Moses, Tanenbaum Nicole, Dougherty Jeanette, Long Sherea, D'Andrea Kurt, Hamilton Jacob T, McLaughlin Maura, Williams Justine C, Adamski Sharon, Kuthuru Oliva, Drapeau Elizabeth M, Davenport Miles P, Hensley Scott E, Bates Paul, Greenplate Allison R, Wherry E John
Institute for Immunology, University of Pennsylvania Perelman School of Medicine; Philadelphia, PA, USA.
Immune Health, University of Pennsylvania Perelman School of Medicine; Philadelphia, PA, USAs.
bioRxiv. 2022 Feb 22:2022.02.20.481163. doi: 10.1101/2022.02.20.481163.
Despite a clear role in protective immunity, the durability and quality of antibody and memory B cell responses induced by mRNA vaccination, particularly by a 3 dose of vaccine, remains unclear. Here, we examined antibody and memory B cell responses in a cohort of individuals sampled longitudinally for ∼9-10 months after the primary 2-dose mRNA vaccine series, as well as for ∼3 months after a 3 mRNA vaccine dose. Notably, antibody decay slowed significantly between 6- and 9-months post-primary vaccination, essentially stabilizing at the time of the 3 dose. Antibody quality also continued to improve for at least 9 months after primary 2-dose vaccination. Spike- and RBD-specific memory B cells were stable through 9 months post-vaccination with no evidence of decline over time, and ∼40-50% of RBD-specific memory B cells were capable of simultaneously recognizing the Alpha, Beta, Delta, and Omicron variants. Omicron-binding memory B cells induced by the first 2 doses of mRNA vaccine were boosted significantly by a 3rd dose and the magnitude of this boosting was similar to memory B cells specific for other variants. Pre-3 dose memory B cell frequencies correlated with the increase in neutralizing antibody titers after the 3 dose. In contrast, pre-3 dose antibody titers inversely correlated with the fold-change of antibody boosting, suggesting that high levels of circulating antibodies may limit reactivation of immunological memory and constrain further antibody boosting by mRNA vaccines. These data provide a deeper understanding of how the quantity and quality of antibody and memory B cell responses change over time and number of antigen exposures. These data also provide insight into potential immune dynamics following recall responses to additional vaccine doses or post-vaccination infections.
尽管在保护性免疫中发挥着明确作用，但mRNA疫苗诱导的抗体和记忆B细胞反应的持久性和质量，尤其是3剂疫苗诱导的反应，仍不清楚。在此，我们在一组个体中检测了抗体和记忆B细胞反应，这些个体在初次2剂mRNA疫苗系列接种后纵向采样约9-10个月，以及在接种3剂mRNA疫苗后约3个月。值得注意的是，初次接种疫苗后6至9个月期间抗体衰减显著减缓，在接种第3剂时基本稳定。初次2剂接种后至少9个月，抗体质量也持续改善。接种疫苗后9个月内，刺突蛋白和受体结合域（RBD）特异性记忆B细胞保持稳定，没有随时间下降的迹象，约40-50%的RBD特异性记忆B细胞能够同时识别阿尔法、贝塔、德尔塔和奥密克戎变体。第3剂疫苗显著增强了前2剂mRNA疫苗诱导的奥密克戎结合记忆B细胞，这种增强的幅度与针对其他变体的记忆B细胞相似。接种第3剂前的记忆B细胞频率与接种第3剂后中和抗体滴度的增加相关。相比之下，接种第3剂前的抗体滴度与抗体增强倍数呈负相关，这表明高水平的循环抗体可能会限制免疫记忆的重新激活，并抑制mRNA疫苗进一步增强抗体。这些数据让我们更深入地了解了抗体和记忆B细胞反应的数量和质量如何随时间和抗原暴露次数而变化。这些数据还为对额外疫苗剂量的回忆反应或接种疫苗后感染后的潜在免疫动态提供了见解。
