An extended SARS-CoV-2 mRNA vaccine prime-boost interval enhances B cell immunity with limited impact on T cells

Abstract

Spacing the first two doses of SARS-CoV-2 mRNA vaccines beyond 3-4weeks raised initial concerns about vaccine efficacy. While studies have since shown that long-interval regimens induce robust antibody responses, their impact on B and Tcell immunity is poorly known. Here, we compare SARS-CoV-2 naive donors B and Tcell responses to two mRNA vaccine doses administered 3-4 versus 16weeks apart. After boost, the longer interval results in a higher magnitude and a more mature phenotype of RBD-specific B cells. While the two geographically distinct cohorts present quantitative and qualitative differences in Tcell responses at baseline and after priming, the second dose led to convergent features with overall similar magnitude, phenotype, and function of CD4+ and CD8+ Tcell responses at post-boost memory time points. Therefore, compared to standard regimens, a 16-week interval has a favorable impact on the B cell compartment but minimally affects Tcell immunity.