This is a summary, written by members of the CITF Secretariat, of:

Datwani S, Kalikawe R, Mwimanzi F, Speckmaier S, Liang R, Sang Y, Waterworth R, Yaseen F, Lapointe HR, Barad E, DeMarco ML, Holmes DT, Simons J, Montaner JSG, Romney MG, Brumme ZL, Brockman MA. Dynamics of T-cell responses following COVID-19 mRNA vaccination and breakthrough infection in older adults. medRxiv 2023.07.14.23292660; doi:

The results and/or conclusions contained in the research do not necessarily reflect the views of all CITF members.

A CITF-funded study, published in preprint and not yet peer-reviewed, found that adults, including older adults (65-93 years), mount robust T-cell responses to two- and three-dose COVID-19 mRNA vaccination. A following breakthrough infection boosts them even further. The study was led by Dr. Mark Brockman (Simon Fraser University) in collaboration with Drs. Marc Romney (St. Paul’s Hospital, Providence Healthcare) and Zabrina Brumme (Simon Fraser University).

Key findings:

  • A third COVID-19 mRNA vaccine dose significantly boosted spike-specific CD4+ and CD8+ T-cell frequencies to above two-dose levels in both older and younger adults.
  • T-cell frequencies did not significantly differ between older and younger adults after either second or third doses.
  • Older age was not associated with impaired T-cell responses. Instead, the strongest predictors of CD4+ and CD8+ T-cell frequencies after a third dose were the corresponding CD4+ and CD8+ T cell frequencies in individuals after their second dose.
  • Older and younger adults who experienced their first SARS-CoV-2 infection after three-dose vaccination (breakthrough infection) showed significantly higher CD4+ and CD8+ T cell frequencies after infection.
  • Human leukocyte antigen (HLA) class I molecules play a significant role in cellular immune defence against pathogens. The researchers found that people with a specific HLA class I typeHuman leukocyte antigens (HLA) present short pathogen-derived protein fragments (peptide antigens) to T cells. These antigens then act as the targets of cellular immune defences. Many different HLA types are found in the human population, allowing different individuals to generate distinct immune responses., known as HLA-A*02:03 had higher post-vaccination CD8+ T-cell frequencies. This may be due to the ability of HLA-A*02:03 to present more targets from SARS-CoV-2 spike to CD8+ T-cells.

The researchers examined spike-specific CD4+ and CD8+ T cell responses against the ancestral SARS-CoV-2 strain after two and three vaccine doses in 90 individuals. This included 40 older adults with a median age of 79 years and 50 younger healthcare workers with a median age of 39 years. 24 individuals had a breakthrough infection (including eight older adults) after their third vaccine dose. None of the participants had experienced COVID-19 prior to vaccination.

This study shows that adults of all ages develop higher frequencies of spike-specific CD4+ and CD8+ T cells with repeated exposure to SARS-CoV-2 spike antigen, whether through vaccination or infection. This effect is observed for up to four exposures.