A Long Interval Between Priming and Boosting SARS-CoV-2 mRNA Vaccine Doses Enhances B Cell Responses With Limited Impact on T Cell Immunity

Spacing the first two doses of SARS-CoV-2 mRNA vaccines beyond 3-4 weeks raised initial concerns about vaccine efficacy. While studies have since shown that long-interval regimens induce robust antibody responses, their impact on B and T cell immunity is poorly known. Here, we compare in SARS-CoV-2 naïve donors B and T cell responses to two mRNA vaccine doses administered 3-4 versus 16 weeks apart. After boost, the longer interval results in higher magnitude and a more mature phenotype of RBD-specific B cells. While the two geographically distinct cohorts present quantitative and qualitative differences in T cell responses at baseline and after priming, the second dose led to convergent features with overall similar magnitude, phenotype and function of CD4+ and CD8+ T cell responses at post-boost memory timepoints. Therefore, compared to standard regimens, a 16-week interval has a favorable impact on the B cell compartment but minimally affects T cell immunity.Funding Information: This work was supported by a FRQS Merit Research Scholar award to D.E.K, the Fondation du CHUM, le Ministère de l’Économie et de l’Innovation du Québec, Programme de soutien aux organismes de recherche et d’innovation (to A.F), a CIHR operating grant # 178344 (D.E.K and A.F), a foundation grant #352417 (A.F), a CIHR operating Pandemic and Health Emergencies Research grant #177958 (A.F), and an Exceptional Fund COVID-19 from the Canada Foundation for Innovation (CFI) #41027 to A.F and D.E.K. The Symphony flow cytometer was funded by a John R. Evans Leaders Fund Leader Fund from the Canada Foundation for Innovation (# 37521 to D.E.K) and the Fondation Sclérodermie Québec. A.F. is the recipient of Canada Research Chair on Retroviral Entry no. RCHS0235 950-232424. V.M.L. is supported by a FRQS Junior 1 salary award, G.S by scholarship from the Department of Microbiology, Infectious Disease and Immunology of the University of Montreal. This work was also supported by NIH funds: grants AI108545, AI155577, AI149680, and U19AI082630 (to E.J.W.), the University of Pennsylvania Perelman School of Medicine COVID Fund (to R.R.G. and E.J.W.); the University of Pennsylvania Perelman School of Medicine 21st Century Scholar Fund (to R.R.G.); and the Paul and Daisy Soros Fellowship for New Americans (to R.R.G).Declaration of Interests: A.R.G. is a consultant for Relation Therapeutics. E.J.W. is consulting for or is an advisor for Merck, Marengo, Janssen, Related Sciences, Synthekine, and Surface Oncology. E.J.W. is a founder of Surface Oncology, Danger Bio, and Arsenal Biosciences. The other authors have no conflict of interest to declare.Ethics Approval Statement: All work was conducted in accordance with the Declaration of Helsinki in terms of informed consent and approval by an appropriate institutional board. Blood samples were obtained from donors who consented to participate in this research project at CHUM (19.381). Individuals from the Philadelphia were enrolled in the study with approval from the University of Pennsylvania Institutional Review Board (IRB# 844642).