Cell-Mediated Immunity of mRNA-1283 Vaccine Encoding SARS-CoV-2 Spike Receptor-Binding and N-Terminal Domains in Preclinical and Clinical Studies.

Abstract

Cell-mediated immunity contributes to durable protection against COVID-19. mRNA-1283 vaccine, encoding the receptor-binding and N-terminal domains of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) spike protein, elicits higher neutralizing antibody responses than mRNA-1273, which encodes the full-length spike protein. We report T-cell responses following mRNA-1283 vaccination in preclinical and clinical studies. For the preclinical evaluation, BALB/c mice received a 2-dose primary series of mRNA-1273 (days 1 and 22), followed by 1 dose of mRNA-1283.222 or mRNA-1273.222 (ancestral + BA.4/BA.5; day 63). C57BL/6 mice received mRNA-1283.815 or mRNA-1273.815 (XBB.1.5; days 1 and 22). T-cell analyses were conducted on spleens from all vaccinated BALB/c and C57BL mice (collected on days 77 and 36, respectively). In the clinical setting, a group of adult (≥18 years) participants in a randomized phase 2 trial (NCT05137236) received 1 dose of mRNA-1283 (ancestral SARS-CoV-2), mRNA-1283.211 (ancestral + beta), mRNA-1283.529 (BA.1), or mRNA-1273 (ancestral), and their SARS-CoV-2 S-protein-specific T-cell responses at days 1 (baseline), 29, 181, and 366 postvaccination were measured. In the mice studies, mRNA-1283 elicited potent S1-directed CD4+ and CD8+ T-cell responses. In the phase 2 study, mRNA-1283 increased S1-specific CD4+ and CD8+ Th1 responses at day 29 postvaccination compared with baseline; responses persisted through day 366 and were similar to mRNA-1273 for all tested strains (ancestral, beta, and BA.1). In preclinical and clinical studies, mRNA-1283 induced T-cell responses similar to mRNA-1273.