Severe Acute Respiratory Syndrome Coronavirus 2 Infection Induces Greater T-Cell Responses Compared to Vaccination in Solid Organ Transplant Recipients

• Published in: The Journal of infectious diseases Vol. 224; no. 11; pp. 1849 - 1860
• Main Authors: Ferreira, Victor H, Marinelli, Tina, Ierullo, Matthew, Ku, Terrance, Hall, Victoria G, Majchrzak-Kita, Beata, Kulasingam, Vathany, Humar, Atul, Kumar, Deepali
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01.12.2021
• Subjects: Antigens; CD4 antigen; CD8 antigen; Coronaviruses; COVID-19; COVID-19 - immunology; COVID-19 Vaccines - immunology; Humans; Immunity, Cellular; Infections; Lymphocytes; Lymphocytes T; Major and Brief Reports; Membrane proteins; mRNA; Mycophenolic acid; Nucleocapsids; Organ Transplantation; PD-1 protein; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; T-Lymphocytes - immunology; Transplant Recipients; Vaccination; COVID-19; SARS-CoV-2; T cells; transplantation; vaccination
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jiab542

Abstract T-cell immunity associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or vaccination in solid organ transplant recipients (SOTRs) is poorly understood. To address this, we measured T-cell responses in 50 SOTRs with prior SARS-CoV-2 infection. The majority of patients mounted SARS-CoV-2–specific CD4+ T-cell responses against spike (S), nucleocapsid, and membrane proteins; CD8+ T-cell responses were generated to a lesser extent. CD4+ T-cell responses correlated with antibody levels. Severity of disease and mycophenolate dose were moderately associated with lower proportions of antigen-specific T cells. Relative to nontransplant controls, SOTRs had perturbations in both total and antigen-specific T cells, including higher frequencies of total PD-1+ CD4+ T cells. Vaccinated SOTRs (n = 55) mounted significantly lower proportions of S-specific polyfunctional CD4+ T cells after 2 doses, relative to unvaccinated SOTRs with prior coronavirus disease 2019. Together, these results suggest that SOTRs generate robust T-cell responses following natural infection that correlate with disease severity but generate comparatively lower T-cell responses following mRNA vaccination. Solid organ transplant recipients mount antigen-specific T-cell responses after SARS-CoV-2 infection that correlate with antibodies and disease severity. Compared to natural infection, vaccine responses to 2 doses of mRNA vaccine result in comparably lower frequencies of antigen-specific CD4+ T cells.