Abstract
The use of coronavirus disease 2019 (COVID-19) vaccines will play the major role in helping to end the pandemic that has killed millions worldwide. COVID-19 vaccines have resulted in robust humoral responses and protective efficacy in human trials, but efficacy trials excluded individuals with a prior diagnosis of COVID-19. As a result, little is known about how immune responses induced by mRNA vaccines differ in individuals who recovered from COVID-19. Here, we evaluated longitudinal immune responses to two-dose BNT162b2 mRNA vaccination in 15 adults who had experienced COVID-19, compared to 21 adults who did not have prior COVID-19. Consistent with prior studies of mRNA vaccines, we observed robust cytotoxic CD8+ T cell responses in both cohorts after the second dose. Furthermore, SARS-CoV-2–naive individuals had progressive increases in humoral and antigen-specific antibody-secreting cell (ASC) responses after each dose of vaccine, whereas SARS-CoV-2–experienced individuals demonstrated strong humoral and antigen-specific ASC responses to the first dose but these responses were not further enhanced after the second dose of the vaccine at the time points studied. Together, these data highlight the relevance of immunological history for understanding vaccine immune responses and may have implications for personalizing mRNA vaccination regimens used to prevent COVID-19, including for the deployment of booster shots.
Highlights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused hundreds of millions of infections and millions of deaths worldwide [1]
We found evidence for altered SARS-CoV-2-specific antibody-secreting cell (ASC) induction in circulation and altered humoral responses to vaccination depending on prior history of COVID-19
We opted to look at one week after second vaccination as that was the peak of the humoral response following mRNA vaccination [12, 16, 31]
Summary
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused hundreds of millions of infections and millions of deaths worldwide [1]. Repeated infection has been described [2, 3], resolution of SARS-CoV-2 infection was associated with reduced susceptibility to re-infection in animal models [4] and in humans [5]. It remains unknown how long this protection lasts. Studies with mRNA vaccine candidates against SARS-CoV-2 have induced robust humoral responses against SARS-CoV-2 in animal models [9,10,11] and in humans [12,13,14,15,16,17] and were efficacious in large-scale clinical trials [18, 19]. The full spectrum of immune responses to the vaccines has not been evaluated
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