Abstract
The durability of immune memory after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccination remains unclear. In this study, 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. By contrast, mRNA vaccines generated functional memory B cells that increased from 3 to 6 months postvaccination, 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 preexisting immunity primarily increased antibody levels without substantially altering antibody decay rates. Together, these findings demonstrate robust cellular immune memory to SARS-CoV-2 and its variants for at least 6 months after mRNA vaccination.
Highlights
First release: 14 October 2021 science.org (Page numbers not final at time of first release) 1 production of antibodies, an effective immune response requires the generation of long-lived memory B and T cells. mRNA vaccines induce robust germinal center responses in humans [14, 15], resulting in memory B cells that are specific for both the full-length SARS-CoV-2 Spike protein and the Spike receptor binding domain (RBD) [16,17,18]. mRNA vaccination has been shown to generate Spike-specific memory CD4+ and CD8+ T cell responses [19,20,21,22]
It is unclear how different components of the immune response may benefit from boosting and whether boosting has any effect on the durability of these components. We investigated these key questions by measuring SARS-CoV-2-specific antibody, memory B cell, and memory T cell responses through 6 months post-vaccination in a group of healthy subjects generating primary immune responses to 2 doses of mRNA vaccine compared with a group of SARS-CoV-2 recovered vaccinees generating recall responses from pre-existing immunity
The continued increase in SARS-CoV-2-specific memory B cells between 3 and 6 months post-mRNA vaccination, even as antibody levels declined in the same individuals, suggests that prolonged germinal center reactions [14] continue to generate circulating memory B cells for at least several months following vaccination
Summary
First release: 14 October 2021 science.org (Page numbers not final at time of first release) 1 production of antibodies, an effective immune response requires the generation of long-lived memory B and T cells. mRNA vaccines induce robust germinal center responses in humans [14, 15], resulting in memory B cells that are specific for both the full-length SARS-CoV-2 Spike protein and the Spike receptor binding domain (RBD) [16,17,18]. mRNA vaccination has been shown to generate Spike-specific memory CD4+ and CD8+ T cell responses [19,20,21,22]. The United States and other well-resourced countries have recently announced plans for a third vaccine booster dose, yet information on how pre-existing serological and cellular immunity to SARSCoV-2 is boosted by mRNA vaccination remains limited It is unclear how different components of the immune response may benefit from boosting and whether boosting has any effect on the durability of these components. We investigated these key questions by measuring SARS-CoV-2-specific antibody, memory B cell, and memory T cell responses through 6 months post-vaccination in a group of healthy subjects generating primary immune responses to 2 doses of mRNA vaccine compared with a group of SARS-CoV-2 recovered vaccinees generating recall responses from pre-existing immunity. These analyses provide insights into mRNA vaccine-induced immunological memory and may be relevant for future vaccine strategies, including recommendations for additional booster vaccine doses
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