Background: Three SARS-CoV-2 vaccines, two based on mRNA, BNT162b2 and mRNA-1273, and one based on an adenovirus platform, Ad26.COV2.S, received emergency use authorization by the U.S. Food and Drug Administration in 2020/2021. These vaccines displayed clinical efficacy in initial studies against confirmed COVID-19 of 95.0%, 94.1%, and 66.9%, respectively. Methods: Individuals receiving one of these vaccines were invited to participate in a prospective longitudinal comparative study of immune responses elicited by the three vaccines. In this observational cohort study, humoral responses were evaluated using a SARS-CoV-2 receptor-binding domain (RBD) ELISA and a SARS-CoV-2 virus neutralization assay at 21-32 days and again at 47-64 days following each initial vaccination. Results: The two mRNA-based platforms elicited similar RBD ELISA responses, but significantly higher neutralizing antibody responses were achieved by mRNA-1273. The adenovirus-based vaccine elicited significantly lower RBD ELISA and SARS-CoV-2 virus neutralization activity. IFN-gamma ELISPOT assays were conducted with peripheral blood mononuclear cells obtained 47-64 days after each initial vaccination. The mRNA-1273 vaccine elicited significantly higher spike glycoprotein-specific T cell responses than either the BNT162b2 or the Ad26.COV2.S vaccines. Conclusions: These findings are consistent with published efficacy data for the three vaccines and support the use of neutralizing antibody titers as a correlate of protection against symptomatic COVID-19.

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.