The Journal of infectious diseases · 2026
Cell-Mediated Immunity of mRNA-1283 Vaccine Encoding SARS-CoV-2 Spike Receptor-Binding and N-Terminal Domains in Preclinical and Clinical Studies.
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Freyn Alec W, Budigi Yadunanda, Girard Bethany, Santos Genesis, Harmon Cathal, Hasan Md Mahmudul, McGrath Shannon, Paila Yamuna D, Carfi Andrea, Edwards Darin, Wahid Rahnuma, Das Rituparna, Chalkias Spyros
Аннотация
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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).
CONCLUSIONS: In preclinical and clinical studies, mRNA-1283 induced T-cell responses similar to mRNA-1273.
METHODS: 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.
RESULTS: 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).
CONCLUSIONS: In preclinical and clinical studies, mRNA-1283 induced T-cell responses similar to mRNA-1273.