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, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA; Immune Health, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Institute for Immunology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA; Immune Health, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Cell. 2022 May 26;185(11):1875-1887.e8. doi: 10.1016/j.cell.2022.04.009. Epub 2022 Apr 8.
We examined antibody and memory B cell responses longitudinally for ∼9-10 months after primary 2-dose SARS-CoV-2 mRNA vaccination and 3 months after a 3rd dose. Antibody decay stabilized between 6 and 9 months, and antibody quality continued to improve for at least 9 months after 2-dose vaccination. Spike- and RBD-specific memory B cells remained durable over time, and 40%-50% of RBD-specific memory B cells simultaneously bound the Alpha, Beta, Delta, and Omicron variants. Omicron-binding memory B cells were efficiently reactivated by a 3rd dose of wild-type vaccine and correlated with the corresponding increase in neutralizing antibody titers. In contrast, pre-3rd dose antibody titers inversely correlated with the fold-change of antibody boosting, suggesting that high levels of circulating antibodies may limit the added protection afforded by repeat short interval boosting. These data provide insight into the quantity and quality of mRNA-vaccine-induced immunity over time through 3 or more antigen exposures.
我们在初次接种2剂SARS-CoV-2 mRNA疫苗后约9至10个月以及接种第3剂疫苗后3个月对抗体和记忆B细胞反应进行了纵向研究。抗体衰减在6至9个月时趋于稳定，且在2剂疫苗接种后至少9个月内抗体质量持续改善。刺突蛋白和受体结合域（RBD）特异性记忆B细胞随时间推移保持持久，且40%至50%的RBD特异性记忆B细胞同时与阿尔法、贝塔、德尔塔和奥密克戎变体结合。奥密克戎结合记忆B细胞通过第3剂野生型疫苗被有效重新激活，并与中和抗体滴度的相应增加相关。相比之下，第3剂疫苗接种前的抗体滴度与抗体增强倍数呈负相关，表明高水平的循环抗体可能会限制短间隔重复加强接种所提供的额外保护。这些数据通过3次或更多次抗原暴露，深入了解了mRNA疫苗诱导的免疫随时间推移的数量和质量。
