Comparative analysis of human immune responses following SARS-CoV-2 vaccination with BNT162b2, mRNA-1273, or Ad26.COV2.S

Abstract

SARS-CoV-2 vaccines BNT162b2, mRNA-1273, and Ad26.COV2.S received emergency use authorization by the U.S. Food and Drug Administration in 2020/2021. Individuals being vaccinated were invited to participate in a prospective longitudinal comparative study of immune responses elicited by the three vaccines. In this observational cohort study, immune responses were evaluated using a SARS-CoV-2 spike protein receptor-binding domain ELISA, SARS-CoV-2 virus neutralization assays and an IFN- γ ELISPOT assay at various times over six months following initial vaccination. mRNA-based vaccines elicited higher magnitude humoral responses than Ad26.COV2.S; mRNA-1273 elicited the most durable humoral response, and all humoral responses waned over time. Neutralizing antibodies against the Delta variant were of lower magnitude than the wild-type strain for all three vaccines. mRNA-1273 initially elicited the greatest magnitude of T cell response, but this declined by 6 months. Declining immunity over time supports the use of booster dosing, especially in the setting of emerging variants.

Fig. 1. RBD ELISA titers amongst vaccine recipients.

Plasma from each timepoint was tested by an RBD ELISA and then converted to WHO BAU/mL. Each data point is shown, the geometric mean and geometric standard deviation are plotted. The dotted line is the limit of detection of the assay (WHO BAU/mL of 28). Statistically significant differences using a mixed effects model with the Geisser-Greenhouse correction for unequal variance and Holm-Sidak multiple comparison test are noted by the respective p value.

Fig. 2. SARS-CoV-2 neutralization amongst vaccine recipients.

Plasma from each timepoint was tested by a SARS-CoV-2 neutralization assay using a WT parental strain (a, c) or the Delta variant (b, d). FRNT₅₀ data were converted to WHO IU/mL (a, b). Data are also shown as the percent of neutralization of input virus achieved at a 1:20 dilution of plasma (c, d). Each data point is shown, the geometric mean and geometric standard deviation (a, b) or mean and standard deviation (c, d) are plotted. The limit of detection for the FRNT₅₀ assay is a WHO IU/mL titer of 51, indicated by a dotted line. Statistically significant differences using a mixed effects model with the Geisser-Greenhouse correction for unequal variance and Holm-Sidak multiple comparison test are noted by the respective p value.

Fig. 3. SARS-CoV-2 spike protein-specific T cell responses amongst vaccine recipients.

PBMCs from the visit 3 and 4 timepoints were tested by an IFN-γ ELISPOT assay. Data are shown as spot forming units (SFU) per 100,000 PBMCs. Each data point is shown, the mean and standard deviation are plotted. Statistically significant differences using a mixed effects model with the Geisser-Greenhouse correction for unequal variance and Holm-Sidak multiple comparison test are noted by the respective p value.