A long interval between priming and boosting SARS-CoV-2 mRNA vaccine doses enhances B cell responses with limited impact on T cell immunity

Abstract

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 naive 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.

A third SARS-CoV-2 mRNA vaccine dose in people receiving hemodialysis overcomes B cell defects but elicits a skewed CD4+T cell profile

“…Consistent with the antibodies (Fig. S1A) and unlike CI (Nicolas et al, 2022), a long interval in HD L did not improve the generation of the RBD + B cell pool (Fig. S1C).…”

“…These features were reported in kidney transplant recipients and dialysis patients (Lederer et al, 2022; Rincon-Arevalo et al, 2021) and attributed to chronic inflammation caused by uremia toxins, along with defects of innate and T cell immunity (Betjes, 2020; Cohen, 2020; Girndt et al, 2020; Valentini et al, 2022). We also observed incomplete B cell maturation in a cohort of CI vaccinated with the standard 3-week short-interval regimen of mRNA vaccine (Nicolas et al, 2022), and thus cannot univocally delineate such defects in the 5-week interval regimen applied to the HD S cohort.…”

“…1D, Fig. S1B) (Nayrac et al, 2022; Nicolas et al, 2022). We observed differences in both magnitude and longitudinal trajectories of B cell responses between cohorts (Fig.…”

“…Some public health agencies delayed the recommended interval between doses to increase population coverage during initial vaccine scarcity (Paltiel et al, 2021; Tuite et al, 2021). Studies in low-risk individuals subsequently showed that a longer interval between the first two doses enhanced humoral responses (Grunau et al, 2022; Hall et al, 2022; Parry et al, 2022; Tauzin et al, 2022a), and increased specific B cell responses and maturation, with little impact on T cells (Hall et al, 2022; Nicolas et al, 2022; Payne et al, 2021).…”

Recent SARS-CoV-2 infection abrogates antibody and B-cell responses to booster vaccination

“…Added to the increasing complexities associated with effects of infection and re-infection histories are challenges associated with timing of vaccines and how repeated boosting, whether through vaccination or infection, affects the magnitude and durability of protective immunity. Previous findings from primary two-dose mRNA vaccines suggest that an extended interval between doses increases neutralizing antibody and cellular responses (Payne et al, 2021), especially B-cell responses (Nicolas et al, 2022). However, as exposures to SARS-CoV-2 increase, whether through vaccination, infection, or both, it is unclear how timing between exposures modulates these responses.…”