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 rsponses following COVID-19 mRNA vaccination and breakthrough infection in older adults. Pathogens and Immunity; 2023 Nov 17. doi: https://doi.org/10.20411/pai.v8i1.613.

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 Pathogens and Immunity, found that adults 65 years and older show strong CD4+Cells that play a central role in the immune system in the generation of B cells and antibody responses. and CD8+Cytotoxic cells that recognize and eliminate virus-infected cells. T-cell responses after receiving two COVID-19 mRNA vaccine doses, which increased significantly after the third dose. The older adults’ T-cell immune responses were comparable in magnitude to those of healthcare workers under 50 years of age. A subsequent breakthrough infection further enhanced T-cell responses among those who had been vaccinated. This study was led by Dr. Mark Brockman (University of British Columbia) in collaboration with Dr. Zabrina Brumme (Simon Fraser University) and Dr. Marc Romney (University of British Columbia).

Key findings:

  • Individuals who received a third COVID-19 vaccine dose had significantly increased SARS-CoV-2 spike-specific CD4+ and CD8+ T-cell frequencies, compared to responses after two doses. These T-cell frequencies did not differ between older and younger adults after either dose.
  • Analyses adjusting for sociodemographic factors (age, sex at birth, race), health, and vaccine-related variables confirmed that older age was not associated with differences in vaccine-induced T-cell responses.
  • The strongest predictors of SARS-CoV-2 spike-specific CD4+ and CD8+ T-cell frequencies following three vaccine doses were the frequencies of spike-specific T-cell responses following two vaccine doses.
  • Individuals who had received three vaccine doses and experienced a breakthrough Omicron BA.1/BA.2 infection had significantly increased CD4+ and CD8+ T-cell frequencies, and these frequencies were similar in older and younger adults.
  • In exploratory analyses, following three vaccine doses, individuals who expressed the human leukocyte antigen (HLA-A)HLA genes play a role in the immune system by providing instructions for the production of proteins that help the body recognize and fight off infections. *02:03 genetic marker had higher post-vaccination SARS-CoV-2 spike-specific CD8+ T-cell frequencies. This could be because there are numerous strong-binding HLA-A*02:03-specific CD8+ T-cell epitopesAn epitope is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. in the SARS-CoV-2 spike protein.

In conclusion, the study suggests that encountering the COVID-19 spike antigen multiple times, either through vaccination or breakthrough infection following vaccination, results in higher T-cell frequencies in adults of all ages with older age not associated with impaired cellular responses. These findings highlight the importance of ongoing vaccination efforts, including encouraging individuals to stay up to date with booster doses.

This study included 50 healthcare workers (HCW) aged 50 and under (median age 39) and 40 older adults aged 65 and older (median age 79) in British Columbia who had remained COVID-19 naïve until at least one month after their third COVID-19 mRNA vaccine dose.