Longitudinal Evaluation of Severe Acute Respiratory Syndrome Coronavirus 2 T-Cell Immunity Over 2 Years Following Vaccination and Infection

J Infect Dis. 2024 Sep 23;230(3):e605-e615. doi: 10.1093/infdis/jiae215.

Abstract

Background: Within a year of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, vaccines inducing a robust humoral and cellular immune response were implemented worldwide. However, emergence of novel variants and waning vaccine-induced immunity led to implementation of additional vaccine boosters.

Methods: This prospective study evaluated the temporal profile of cellular and serological responses in a cohort of 639 SARS-CoV-2-vaccinated participants, of whom a large proportion experienced a SARS-CoV-2 infection. All participants were infection naïve at the time of their first vaccine dose. Proportions of SARS-CoV-2 spike-specific T cells were determined after each vaccine dose using the activation-induced marker assay, while levels of circulating SARS-CoV-2 antibodies were determined by the Meso Scale serology assay.

Results: We found a significant increase in SARS-CoV-2 spike-specific CD4+ and CD8+ T-cell responses following the third dose of a SARS-CoV-2 messenger RNA vaccine as well as enhanced CD8+ T-cell responses after the fourth dose. Furthermore, increased age was associated with a poorer response. Finally, we observed that SARS-CoV-2 infection boosts both the cellular and humoral immune response, relative to vaccine-induced immunity alone.

Conclusions: Our findings highlight the boosting effect on T-cell immunity of repeated vaccine administration. The combination of multiple vaccine doses and SARS-CoV-2 infections maintains population T-cell immunity, although with reduced levels in the elderly.

Keywords: COVID-19; Spike-specific T cells; cellular response; hybrid immunity; longitudinal study; vaccination.

MeSH terms

  • Adult
  • Aged
  • Antibodies, Viral* / blood
  • CD4-Positive T-Lymphocytes* / immunology
  • CD8-Positive T-Lymphocytes* / immunology
  • COVID-19 Vaccines* / administration & dosage
  • COVID-19 Vaccines* / immunology
  • COVID-19* / immunology
  • COVID-19* / prevention & control
  • Female
  • Humans
  • Immunity, Cellular
  • Immunization, Secondary
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Prospective Studies
  • SARS-CoV-2* / immunology
  • Spike Glycoprotein, Coronavirus* / immunology
  • T-Lymphocytes / immunology
  • Vaccination
  • Young Adult

Substances

  • Antibodies, Viral
  • COVID-19 Vaccines
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2