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Updated: Jun 28, 2025

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Altered pre-existing SARS-CoV-2-specific T cell responses in elderly individuals.

Naoyuki Taira1, Sakura Toguchi1, Mio Miyagi1

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|April 15, 2024
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Pre-existing T cell immunity to SARS-CoV-2 varies with age, with elderly individuals showing lower responses to Spike and Nucleoprotein antigens. However, T cell responses to the Membrane protein remain strong across age groups, suggesting potential for vaccine development.

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Area of Science:

  • Immunology
  • Virology
  • Gerontology

Background:

  • Pre-existing SARS-CoV-2-specific T cells, not antibodies, are found in some unexposed individuals, potentially influencing COVID-19 clinical outcomes.
  • Age is a known risk factor for COVID-19, but its impact on SARS-CoV-2-specific T cell responses is not well understood.

Purpose of the Study:

  • To investigate the effect of age on pre-existing and infection-induced SARS-CoV-2-specific T cell responses.
  • To identify viral antigens that elicit age-independent T cell responses for potential vaccine strategies.

Main Methods:

  • Comparative analysis of T cell responses to SARS-CoV-2 Spike (S), Nucleoprotein (N), and Membrane (M) proteins in young and elderly donors.
  • Assessment of both pre-existing T cell immunity in unexposed individuals and T cell responses post-SARS-CoV-2 infection.

Main Results:

  • Elderly donors (>70 years) exhibited significantly lower pre-existing T cell responses to S and N proteins compared to young donors.
  • Substantial pre-existing T cell responses to the M protein were observed in both young and elderly individuals.
  • Following SARS-CoV-2 infection, T cell responses to S, N, and M proteins were comparable across all age groups.

Conclusions:

  • SARS-CoV-2 infection elicits T cell responses to various antigens irrespective of age.
  • The repertoire of target antigens for long-lived memory T cells against SARS-CoV-2 may diminish with age.
  • T cell responses to specific viral proteins like M are maintained with age, offering a promising avenue for developing effective vaccines for the elderly.