Safety and Immunogenicity of SARS-CoV-2 Spike Receptor-Binding Domain and N-Terminal Domain mRNA Vaccine

Abstract

BACKGROUND: mRNA-1283 is an investigational coronavirus disease 2019 (COVID-19) mRNA vaccine encoding the receptor-binding and N-terminal domains of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein in contrast to the original mRNA-1273 vaccine, which encodes the full-length spike protein. METHODS: A phase 2a, dose-ranging, observer-blind, randomized study conducted in adults (aged ≥18 years) previously vaccinated with mRNA-1273 evaluated the safety and immunogenicity of a single dose of mRNA-1283 (2.5, 5, and 10 µg) and its bivalent formulation, mRNA-1283.211 (5 and 10 µg; encoding original SARS-CoV-2 and Beta) against the comparator mRNA-1273 vaccine, 50 µg (part A). A subsequent, open-label study (part B) evaluated the safety and immunogenicity of a monovalent Omicron BA.1 vaccine, mRNA-1283.529 (5 and 10 µg). RESULTS: A total of 340 participants were randomized in part A, and 200 participants were enrolled in part B. All dose levels of mRNA-1283 vaccines were well tolerated and increased the neutralizing antibody (nAb) responses at day 29 compared to baseline against SARS-CoV-2 D614G and Beta. The nAb responses elicited by mRNA-1283 were higher than those elicited by mRNA-1273. mRNA-1283.529 (part B) increased nAb at day 29 against Omicron BA.1. Antibody responses remained detectable for a year postvaccination. CONCLUSIONS: mRNA-1283 was well tolerated and exhibited improved immunogenicity compared to mRNA-1273. CLINICAL TRIALS REGISTRATION: NCT05137236.