mRNA-1273 COVID-19 vaccine induces CD4 + T-cell responses among solid organ transplant recipients

Bethany Girard ^1* Amparo Figueroa ¹ Stephen C De Rosa ² M. Juliana McElrath ² Jamil R. Azzi ³ Dina Stolman ¹ Uma Siangphoe ¹ Elizabeth de Windt ¹ Jacqueline M Miller ¹ Rituparna Das ¹ Frances Priddy ¹

• ¹ Moderna Inc, Cambridge, United States
• ² Fred Hutchinson Cancer Center, Seattle, Washington, United States
• ³ Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States

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 3 100-µg doses of mRNA-1273; immunocompetent participants received 2 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 + 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 + T-cell responses were below those observed for Th-1; CD8 + 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.Conclusions: Overall, a 3-dose mRNA-1273 primary series elicited Th-1-biased CD4 + T-cell responses among SOTRs that were improved with an additional dose.