mRNA vaccines induce durable immune memory to SARS-CoV-2 and variants of concern

Goel, Rishi R; Painter, Mark M; Apostolidis, Sokratis A; Mathew, Divij; Meng, Wenzhao; Rosenfeld, Aaron M; Lundgreen, Kendall A; Reynaldi, Arnold; Khoury, David S; Pattekar, Ajinkya; Gouma, Sigrid; Kuri-Cervantes, Leticia; Hicks, Philip; Dysinger, Sarah; Hicks, Amanda; Sharma, Harsh; Herring, Sarah; Korte, Scott; Baxter, Amy E; Oldridge, Derek A; Giles, Josephine R; Weirick, Madison E; McAllister, Christopher M; Awofolaju, Moses; Tanenbaum, Nicole; Drapeau, Elizabeth M; Dougherty, Jeanette; Long, Sherea; D'Andrea, Kurt; Hamilton, Jacob T; McLaughlin, Maura; Williams, Justine C; Adamski, Sharon; Kuthuru, Oliva; Frank, Ian; Betts, Michael R; Vella, Laura A; Grifoni, Alba; Weiskopf, Daniela; Sette, Alessandro; Hensley, Scott E; Davenport, Miles P; Bates, Paul; Luning Prak, Eline T; Greenplate, Allison R; Wherry, E John; Adamski, S; Alam, Z; Addison, M M; Byrne, K T

The durability of immune memory after SARS-CoV-2 mRNA vaccination remains unclear. Here, we longitudinally profiled vaccine responses in SARS-CoV-2 naïve and recovered individuals for 6 months after vaccination. Antibodies declined from peak levels but remained detectable in most subjects at 6 months. We found mRNA vaccines generated functional memory B cells that increased from 3-6 months post-vaccination, with the majority of these cells cross-binding the Alpha, Beta, and Delta variants. mRNA vaccination further induced antigen-specific CD4+ and CD8+ T cells, and early CD4+ T cell responses correlated with long-term humoral immunity. Recall responses to vaccination in individuals with pre-existing immunity primarily increased antibody levels without substantially altering antibody decay rates. Together, these findings demonstrate robust cellular immune memory to SARS-CoV-2 and variants for at least 6 months after mRNA vaccination.