Dynamics of T-cell responses following COVID-19 mRNA vaccination and breakthrough infection in older adults

Older adults typically have weaker antibody responses to COVID-19 vaccines, but their T-cell responses are less understood. This study examines T-cell frequencies following two and three doses of COVID-19 mRNA vaccination in 40 older adults (median age 79 years) and 50 younger healthcare workers (median age 39 years) using an activation-induced marker assay. None of the participants had been infected with COVID-19.

T-cell responses were further assessed in 24 participants, including eight older adults, who subsequently experienced their first SARS-CoV-2 breakthrough infection.

Key Findings:

• Third Vaccine Dose: Both older and younger adults showed a significant increase in specific T-cell frequencies after receiving a third COVID-19 mRNA vaccine dose compared to after two doses.
• Age Comparison: T-cell frequencies did not significantly differ between older and younger adults after either two or three COVID-19 vaccine doses.
• Predictors of Response: After adjusting for sociodemographic, health, and vaccine-related variables, it was confirmed that older age was not associated with impaired cellular responses. The strongest predictors of CD4+ and CD8+ T-cell frequencies after the third dose were their corresponding post-second-dose frequencies.
• Breakthrough Infections: Both older and younger adults who had a breakthrough COVID-19 infection showed a significant increase in T-cell frequencies to similar levels.
• Genetic Factors: An exploratory analysis suggested that people with a specific genetic marker (HLA-A*02:03) might have higher CD8 T-cell frequencies, potentially due to better recognition of parts of the spike protein.

In summary, older adults generate strong T-cell responses to COVID-19 mRNA vaccines, similar to younger adults. These responses are further enhanced following a breakthrough infection, indicating that older adults can mount a robust immune response beyond just antibody production.

This study highlights the effectiveness of mRNA vaccines in boosting cellular immunity in older adults, which is crucial for long-term protection against COVID-19.

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