Spike-Specific CD4+ and CD8+ T Cell Memory Formation and 12-Month Durability After mRNA-1273 Booster Vaccination in Immunocompromised Adults

This study investigates spike-specific CD4+ and CD8+ T lymphocyte memory magnitude, phenotype, and 12-month durability following mRNA-1273 booster vaccination in immunocompromised adults versus healthy controls within the context of vaccinology and clinical immunology, an area of growing scientific importance given its implications for booster vaccination timing recommendations for immunocompromised populations and cellular immunomonitoring strategies for vulnerable vaccine recipients. Using intracellular cytokine staining and activation-induced marker assay measuring spike-specific T cell responses at pre-boost, day 14, day 90, and 12-month timepoints by flow cytometry, we examine mRNA-1273 spike antigen expression driving CD4+ T follicular helper priming of germinal center B cells and CD8+ cytotoxic T cell expansion, with immunosuppression attenuating but not eliminating memory formation in 248 participants: 84 solid organ transplant recipients, 80 hematologic malignancy patients, 48 HIV-infected adults, and 36 healthy controls; all received mRNA-1273 booster drawn from academic transplant, oncology, and HIV clinics at Grandview University Medical Center with PBMC collection and cryopreservation for batch flow cytometry. Results indicate that mRNA-1273 booster generates spike-specific CD4+ responses in 78.6% of immunocompromised participants (versus 97.2% healthy controls) with 12-month response persistence in 62.4% of responders across immunocompromised groups (p < 0.001), with 78.6% CD4+ response rate in immunocompromised vs. 97.2% healthy controls; 62.4% 12-month persistence as the primary quantitative benchmark. Concordance between primary and confirmatory measurement approaches exceeded 93%, validating the analytical framework. These findings contribute empirically to vaccinology and clinical immunology and carry actionable implications for the design of programs and policies targeting booster vaccination timing recommendations for immunocompromised populations and cellular immunomonitoring strategies for vulnerable vaccine recipients.