COVID-19 mRNA or viral vector vaccine type and subject sex influence the SARS-CoV-2 T-cell response

• Published in: Vaccine Vol. 61; p. 127420
• Main Authors: Tong, Sherry, Litwin, Sean M., Epel, Elissa S., Lin, Jue, Drury, Stacy S., Hecht, Frederick M., Robinson, James E., Prather, Aric A., Norton, Elizabeth B.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 13.08.2025; Elsevier Limited
• Subjects: Adult; Allergy and Immunology; Antibodies; Antibodies, Neutralizing - blood; Antibodies, Neutralizing - immunology; Antibodies, Viral - blood; Antibodies, Viral - immunology; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Cells; COVID-19; COVID-19 - immunology; COVID-19 - prevention & control; COVID-19 vaccine; COVID-19 vaccines; COVID-19 Vaccines - immunology; Cytokines; Cytokines - immunology; Cytokines - metabolism; FDA approval; Female; Humans; Immune response; Immune response (cell-mediated); Immune system; Immunity (Disease); Immunity, Cellular; Immunological memory; Immunoregulation; Infections; Lymphocytes T; Male; Middle Aged; mRNA; mRNA vaccines; Proteins; Questionnaires; SARS-CoV-2; SARS-CoV-2 - immunology; Severe acute respiratory syndrome coronavirus 2; Sex differences; Sex Factors; Sociodemographics; Spike Glycoprotein, Coronavirus - immunology; Stains & staining; T-cell; Vaccination; Vaccines; Vectors (Biology); Viral diseases; Viral infections; Young Adult; United States > US; San Francisco California; California; COVID-19 vaccine; Sex differences; SARS-CoV-2; T-cell
• ISSN: 0264-410X; 1873-2518; 1873-2518
• DOI: 10.1016/j.vaccine.2025.127420

Severe SARS-CoV-2 infection has been partially controlled by vaccination, though issues in duration and breadth of protection remain. Few studies investigate factors driving diversity in the cellular immune response to vaccination. Here, we evaluated T-cell immunity in 60 healthy adults and its relationship to vaccine and subject-specific variables. CD4 and CD8 T-cells from COVID-19 vaccinated subjects expressed spike-specific activation-induced markers (AIM+) and cytokines. Overall, AIM+ CD8 T-cells correlated best with neutralizing antibodies and were more strongly expressed by females than males. Unique patterns in CD4 T-regulatory cells, cytokine profiles, and central and effector memory subsets were observed between Moderna, Pfizer, and Janssen vaccinees and by subject-specific factors. Sex differences outweighed differences in BMI and age. Thus, COVID-19 vaccine type and subject sex impacted the magnitude and quality of the spike-specific T-cell response. These results help explain differences in durability and memory between mRNA and adenovirus vector based COVID-19 vaccines and suggest targets for improved vaccine design.