Your browser doesn't support javascript.
TEMPORAL ASSOCIATIONS of B and T CELL IMMUNITY in A 16-WEEK INTERVAL BNT162b2 REGIMEN
Topics in Antiviral Medicine ; 30(1 SUPPL):90-91, 2022.
Article in English | EMBASE | ID: covidwho-1880636
ABSTRACT

Background:

Spacing of the BNT162b2 mRNA doses beyond the standard 3-week interval raised concerns about vaccine efficacy. We longitudinally analyzed B cell, T cell and humoral responses to two BNT162b2 mRNA doses administered 16 weeks apart in 43 SARS-CoV-2 naïve and previously-infected (PI) donors. We examined blood samples at five time points from baseline to 4 months post second dose.

Methods:

We used high-parameter flow cytometry to study i) receptor binding domain (RBD)-specific B cells;ii) Spike (S)-specific CD4 and CD8 T cells by activation-induced marker (AIM) assay;iii) S-specific CD4 and CD8 T cells by intracellular staining (ICS) assay. We measured humoral responses by ELISA, neutralization and ADCC assays. We did supervised and unsupervised (FlowSOM) analyses of B and T cell subsets, and temporal association analyses.

Results:

We observed partial attrition of B and T cell responses between doses at a memory time point 12 weeks post first dose. RBD-specific B cell kinetics differed between cohorts the first dose led to their robust increase in PI but small magnitude in naïve. The second dose had little effect in PI but briskly expanded RBD-specific B cells in naïve, leading to convergence between cohorts. Robust T cell responses, with a dominance of CD4 over CD8 responses, were universally induced and did not significantly differ in magnitude after either dose, although there was a trend for a gain in CD8 responses after the second dose in naïve. Unsupervised and supervised analyses of S-specific CD4 T cells showed that the first dose was sufficient to generate highly diverse CD4 subsets, including robust populations of follicular T helper cells. The second dose did not elicit new subsets but lead to convergent phenotypic and functional profiles between PI and naïve with qualitative shifts. Integrated analyses of antigen-specific responses showed immune component-specific associations over-time, with early CD4 responses post-first dose (but not at late time points) strongly correlating with B cell responses after the second dose. In contrast, CD8 responses post second dose correlated with CD4 responses at the same time point.

Conclusion:

The 16-week interval schedule is associated with robust, multi-faceted recall cellular responses after the second dose, consistent with highly functional immune memory. The early induction of robust CD4 responses and their associations with longer-term B cell and humoral immunity support their central role in the efficacy of this vaccine regimen.
Keywords
Search on Google
Collection: Databases of international organizations Database: EMBASE Language: English Journal: Topics in Antiviral Medicine Year: 2022 Document Type: Article

Similar

MEDLINE

...
LILACS

LIS

Search on Google
Collection: Databases of international organizations Database: EMBASE Language: English Journal: Topics in Antiviral Medicine Year: 2022 Document Type: Article