Aging and Viral Evolution Impair Immunity Against Dominant Pan-Coronavirus-Reactive T Cell Epitope

Area of Science:

• Immunology
• Virology
• Gerontology

Background:

• Immune evasion by SARS-CoV-2 escape mutations compromises vaccine effectiveness.
• Pan-coronavirus immunity offers potential for durable protection but remains understudied.
• Understanding age-related immune responses is crucial for long-term COVID-19 protection.

Purpose of the Study:

• To investigate the impact of age, SARS-CoV-2 mutations, and vaccination regimens on pan-coronavirus-specific immunity.
• To analyze the iCope epitope-reactive cellular (CD4+ T cell) and humoral immune responses.
• To assess the durability of immune protection against SARS-CoV-2 variants in different age groups.

Main Methods:

• Detailed analysis of iCope-reactive cellular and humoral immune responses post-SARS-CoV-2 infection and vaccination.
• Evaluation of immune responses in relation to participant age, specific mutations, and vaccination history (homologous/heterologous).
• Assessment of T cell receptor (TCR) repertoire diversity in older individuals.

Main Results:

• Older individuals exhibited reduced quantity and quality of iCope-reactive CD4+ T cell responses with narrow TCR repertoires.
• Vaccination failed to enhance these T cell responses in older adults.
• Emerging spike mutations further compromised T cell responses in the elderly.
• Pan-coronavirus-reactive humoral immunity was affected by mutations but not by age.

Conclusions:

• A distinct deficiency in pan-coronavirus immunity exists in older individuals, particularly affecting T cell responses.
• This age-related immune deficiency compromises long-term protection against evolving SARS-CoV-2 variants.
• Targeting strategies to bolster pan-coronavirus immunity in the elderly is critical for sustained COVID-19 defense.