tetano
Editor, Senior Moderator
Front Immunol
. 2025 Apr 3:16:1505871.
doi: 10.3389/fimmu.2025.1505871. eCollection 2025. mRNA-1273 COVID-19 vaccine induces CD4+ T-cell responses among solid organ transplant recipients
Bethany Girard[SUP] 1 [/SUP], Amparo L Figueroa[SUP] 1 [/SUP], Stephen C De Rosa[SUP] 2 [/SUP], M Juliana McElrath[SUP] 2 [/SUP], Jamil R Azzi[SUP] 3 [/SUP], Dina Stolman[SUP] 1 [/SUP], Uma Siangphoe[SUP] 1 [/SUP], Elizabeth de Windt[SUP] 1 [/SUP], Jacqueline M Miller[SUP] 1 [/SUP], Rituparna Das[SUP] 1 [/SUP], Frances Priddy[SUP] 1 [/SUP]
Affiliations
Background: Cell-mediated immunity may provide durable protection against severe COVID-19, including among solid organ transplant recipients (SOTRs). This exploratory analysis in the open-label phase 3b trial evaluated cell-mediated immunity of mRNA-1273 in a subset of participants (59 kidney and 33 liver SOTRs; 12 immunocompetent participants).
Methods: In Part A, SOTRs received three 100-µg doses of mRNA-1273; immunocompetent participants received two doses. In Part B, an additional 100-µg dose was offered ≥4 months after the primary series. SARS-CoV-2 spike (S) protein-specific T-cell responses were measured by intracellular cytokine staining and polyfunctionality analyses.
Results: The primary series and additional dose of mRNA-1273 induced S protein-specific CD4[SUP]+[/SUP] T-cell responses exhibiting a Th-1-biased profile in both SOTRs and immunocompetent participants; however, response rates and magnitudes were lower among SOTRs. S protein-specific Th-2 CD4[SUP]+[/SUP] T-cell responses were below those observed for Th-1; CD8[SUP]+[/SUP] T-cell responses were not as robust among SOTRs compared with immunocompetent participants. Kidney SOTRs received multiple immunosuppressants and had lower cell-mediated immunity responses than liver SOTRs. Polyfunctional responses exhibited Th-1 cytokine signatures with ≤5 functional markers reported in SOTRs and immunocompetent participants.
Conclusion: Overall, a three-dose mRNA-1273 primary series elicited Th-1-biased CD4[SUP]+[/SUP] T-cell responses among SOTRs that were improved with an additional dose.
Clinical trial registration: https://beta.clinicaltrials.gov/study/NCT04860297?term=NCT04860297 &rank=1, identifier NCT04860297.
Keywords: COVID-19; cell-mediated immunity; mRNA-1273; solid-organ transplant recipients; vaccine.
. 2025 Apr 3:16:1505871.
doi: 10.3389/fimmu.2025.1505871. eCollection 2025. mRNA-1273 COVID-19 vaccine induces CD4+ T-cell responses among solid organ transplant recipients
Bethany Girard[SUP] 1 [/SUP], Amparo L Figueroa[SUP] 1 [/SUP], Stephen C De Rosa[SUP] 2 [/SUP], M Juliana McElrath[SUP] 2 [/SUP], Jamil R Azzi[SUP] 3 [/SUP], Dina Stolman[SUP] 1 [/SUP], Uma Siangphoe[SUP] 1 [/SUP], Elizabeth de Windt[SUP] 1 [/SUP], Jacqueline M Miller[SUP] 1 [/SUP], Rituparna Das[SUP] 1 [/SUP], Frances Priddy[SUP] 1 [/SUP]
Affiliations
- PMID: 40248714
- PMCID: PMC12004975
- DOI: 10.3389/fimmu.2025.1505871
Background: Cell-mediated immunity may provide durable protection against severe COVID-19, including among solid organ transplant recipients (SOTRs). This exploratory analysis in the open-label phase 3b trial evaluated cell-mediated immunity of mRNA-1273 in a subset of participants (59 kidney and 33 liver SOTRs; 12 immunocompetent participants).
Methods: In Part A, SOTRs received three 100-µg doses of mRNA-1273; immunocompetent participants received two doses. In Part B, an additional 100-µg dose was offered ≥4 months after the primary series. SARS-CoV-2 spike (S) protein-specific T-cell responses were measured by intracellular cytokine staining and polyfunctionality analyses.
Results: The primary series and additional dose of mRNA-1273 induced S protein-specific CD4[SUP]+[/SUP] T-cell responses exhibiting a Th-1-biased profile in both SOTRs and immunocompetent participants; however, response rates and magnitudes were lower among SOTRs. S protein-specific Th-2 CD4[SUP]+[/SUP] T-cell responses were below those observed for Th-1; CD8[SUP]+[/SUP] T-cell responses were not as robust among SOTRs compared with immunocompetent participants. Kidney SOTRs received multiple immunosuppressants and had lower cell-mediated immunity responses than liver SOTRs. Polyfunctional responses exhibited Th-1 cytokine signatures with ≤5 functional markers reported in SOTRs and immunocompetent participants.
Conclusion: Overall, a three-dose mRNA-1273 primary series elicited Th-1-biased CD4[SUP]+[/SUP] T-cell responses among SOTRs that were improved with an additional dose.
Clinical trial registration: https://beta.clinicaltrials.gov/study/NCT04860297?term=NCT04860297 &rank=1, identifier NCT04860297.
Keywords: COVID-19; cell-mediated immunity; mRNA-1273; solid-organ transplant recipients; vaccine.