Evolution of SARS-CoV-2 T cell responses as a function of multiple COVID-19 boosters

https://pubmed.ncbi.nlm.nih.gov/39829792/

created by RadioheadTrader on 22/01/2025 at 06:53 UTC

60 upvotes, 3 top-level comments (showing 3)

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Comment by AutoModerator at 22/01/2025 at 06:53 UTC

1 upvotes, 0 direct replies

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Comment by RadioheadTrader at 22/01/2025 at 06:54 UTC

22 upvotes, 1 direct replies

The long-term effects of repeated COVID-19 vaccinations on adaptive immunity remain incompletely understood. Here, we conducted a comprehensive three-year longitudinal study examining T cell and antibody responses in 78 vaccinated individuals without reported symptomatic infections. We observed distinct dynamics in Spike-specific humoral and cellular immune responses across multiple vaccine doses. While antibody titers incrementally increased and stabilized with each booster, T cell responses rapidly plateaued, maintaining remarkable stability across CD4+ and CD8+ subsets. Notably, approximately 30% of participants showed CD4+ T cell reactivity to non-Spike antigens, consistent with asymptomatic infections. Single-cell RNA sequencing revealed a diverse landscape of Spike-specific T cell phenotypes, with no evidence of increased exhaustion or significant functional impairment. However, qualitative changes were observed in individuals with evidence of asymptomatic infection, exhibiting unique immunological characteristics, including increased frequencies of Th17-like CD4+ T cells and GZMKhi/IFNR CD8+ T cell subsets. Remarkably, repeated vaccinations in this group were associated with a progressive increase in regulatory T cells, potentially indicating a balanced immune response that may mitigate immunopathology. By regularly stimulating T cell memory, boosters contribute to a stable and enhanced immune response, which may provide better protection against symptomatic infections.

Comment by beseeingyou18 at 22/01/2025 at 12:23 UTC

3 upvotes, 1 direct replies

Notably, approximately 30% of participants showed CD4+ T cell reactivity to non-Spike antigens, consistent with asymptomatic infections. Single-cell RNA sequencing revealed a diverse landscape of Spike-specific T cell phenotypes, with no evidence of increased exhaustion or significant functional impairment. However, qualitative changes were observed in individuals with evidence of asymptomatic infection, exhibiting unique immunological characteristics, including increased frequencies of Th17-like CD4+ T cells and GZMKhi/IFNR CD8+ T cell subsets.

I'm wondering if that 30% of people would map to those with Long Covid?

Reactivity to non-spike antigens suggests that the Covid virus may be gone but that something remains which causes this reaction?

In addition, TH17 cells often target the lungs and GZMK is often responsible for inflammation in chronic conditions.

Could this suggest that there are ongoing viral remnants (non-active virus) that remain in the lungs?