Rapid induction of antigen-specific CD4+ T cells is associated with coordinated humoral and cellular immunity to SARS-CoV-2 mRNA vaccination

• Published in: Immunity (Cambridge, Mass.) Vol. 54; no. 9; pp. 2133 - 2142.e3
• Main Authors: Painter, Mark M., Mathew, Divij, Goel, Rishi R., Apostolidis, Sokratis A., Pattekar, Ajinkya, Kuthuru, Oliva, Baxter, Amy E., Herati, Ramin S., Oldridge, Derek A., Gouma, Sigrid, Hicks, Philip, Dysinger, Sarah, Lundgreen, Kendall A., Kuri-Cervantes, Leticia, Adamski, Sharon, Hicks, Amanda, Korte, Scott, Giles, Josephine R., Weirick, Madison E., McAllister, Christopher M., Dougherty, Jeanette, Long, Sherea, D’Andrea, Kurt, Hamilton, Jacob T., Betts, Michael R., Bates, Paul, Hensley, Scott E., Grifoni, Alba, Weiskopf, Daniela, Sette, Alessandro, Greenplate, Allison R., Wherry, E. John
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 14.09.2021
• Subjects: 2019-nCoV Vaccine mRNA-1273; activation induced markers; Adult; AIM; Antibodies, Neutralizing - blood; Antibodies, Viral - blood; Antigens, CD - metabolism; Antigens, Differentiation, T-Lymphocyte - metabolism; BNT162 Vaccine; CD8-Positive T-Lymphocytes - immunology; COVID-19 - immunology; COVID-19 Vaccines - immunology; Female; Humans; Immunity, Cellular; Immunity, Humoral; Immunization, Secondary; Immunologic Memory; immunological memory; Lectins, C-Type - metabolism; Lymphocyte Activation; Male; Middle Aged; mRNA vaccine; Peptides - immunology; SARS-CoV-2; SARS-CoV-2 - physiology; Spike Glycoprotein, Coronavirus - immunology; T cells; T follicular helper; Tfh; Th1; Th1 Cells - immunology; Vaccination; Young Adult; SARS-CoV-2; activation induced markers; AIM; Tfh; immunological memory; T cells; T follicular helper; Th1; mRNA vaccine
• ISSN: 1074-7613; 1097-4180; 1097-4180
• DOI: 10.1016/j.immuni.2021.08.001

SARS-CoV-2 mRNA vaccines have shown remarkable clinical efficacy, but questions remain about the nature and kinetics of T cell priming. We performed longitudinal antigen-specific T cell analyses on healthy SARS-CoV-2-naive and recovered individuals prior to and following mRNA prime and boost vaccination. Vaccination induced rapid antigen-specific CD4+ T cell responses in naive subjects after the first dose, whereas CD8+ T cell responses developed gradually and were variable in magnitude. Vaccine-induced Th1 and Tfh cell responses following the first dose correlated with post-boost CD8+ T cells and neutralizing antibodies, respectively. Integrated analysis revealed coordinated immune responses with distinct trajectories in SARS-CoV-2-naive and recovered individuals. Last, whereas booster vaccination improved T cell responses in SARS-CoV-2-naive subjects, the second dose had little effect in SARS-CoV-2-recovered individuals. These findings highlight the role of rapidly primed CD4+ T cells in coordinating responses to the second vaccine dose in SARS-CoV-2-naive individuals. [Display omitted] •mRNA vaccines generate antigen-specific T cells in a coordinated immune response•Vaccine-induced T cells resemble the durable memory cells primed by infection•Th1 and cTfh cell responses to the first dose correlate with second-dose responses•SARS-CoV-2-recovered individuals benefit from the first but not the second dose SARS-CoV-2 mRNA vaccines have demonstrated remarkable efficacy, but T cell responses to vaccination have not been well studied. In a longitudinal cohort, Painter et al. show that mRNA vaccines activate SARS-CoV-2-specific T cells that could contribute to durable immunity. The findings highlight the central role of T cells in the two-dose vaccine regimen for individuals not previously infected with SARS-CoV-2.