tetano
Editor, Senior Moderator
J Infect Dis
. 2026 Jun 4:jiag248.
doi: 10.1093/infdis/jiag248. Online ahead of print.
Cell-Mediated Immunity of mRNA-1283 Vaccine Encoding SARS-CoV-2 Spike Receptor-Binding and N-Terminal Domains in Preclinical and Clinical Studies
Alec W Freyn[SUP] 1 [/SUP], Yadunanda Budigi[SUP] 1 [/SUP], Bethany Girard[SUP] 1 [/SUP], Genesis Santos[SUP] 1 [/SUP], Cathal Harmon[SUP] 1 [/SUP], Md Mahmudul Hasan[SUP] 1 [/SUP], Shannon McGrath[SUP] 1 [/SUP], Yamuna D Paila[SUP] 1 [/SUP], Andrea Carfi[SUP] 1 [/SUP], Darin Edwards[SUP] 1 [/SUP], Rahnuma Wahid[SUP] 1 [/SUP], Rituparna Das[SUP] 1 [/SUP], Spyros Chalkias[SUP] 1 [/SUP]
Affiliations
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.
Keywords: COVID-19; SARS-CoV-2; T cell; mRNA-1273; mRNA-1283.
. 2026 Jun 4:jiag248.
doi: 10.1093/infdis/jiag248. Online ahead of print.
Cell-Mediated Immunity of mRNA-1283 Vaccine Encoding SARS-CoV-2 Spike Receptor-Binding and N-Terminal Domains in Preclinical and Clinical Studies
Alec W Freyn[SUP] 1 [/SUP], Yadunanda Budigi[SUP] 1 [/SUP], Bethany Girard[SUP] 1 [/SUP], Genesis Santos[SUP] 1 [/SUP], Cathal Harmon[SUP] 1 [/SUP], Md Mahmudul Hasan[SUP] 1 [/SUP], Shannon McGrath[SUP] 1 [/SUP], Yamuna D Paila[SUP] 1 [/SUP], Andrea Carfi[SUP] 1 [/SUP], Darin Edwards[SUP] 1 [/SUP], Rahnuma Wahid[SUP] 1 [/SUP], Rituparna Das[SUP] 1 [/SUP], Spyros Chalkias[SUP] 1 [/SUP]
Affiliations
- PMID: 42240400
- DOI: 10.1093/infdis/jiag248
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.
Keywords: COVID-19; SARS-CoV-2; T cell; mRNA-1273; mRNA-1283.