Immune age is correlated with decreased TCR clonal diversity and antibody response to SARS-CoV-2

Immune response to infection or vaccination is compromised with age. We aimed to examine associations between immune senescence, T and B cell clonal diversity and immunoglobulin G secretion in response to immune challenge in isolated peripheral blood mononuclear cells (PBMC) from people of different chronological ages. We isolated PBMC from 49 individuals categorised into < 35 years and > 60 years age groups. Cells were then challenged with recombinant SARS-CoV-2 spike protein or vehicle and IMMAX score was calculated for each sample from flow cytometry. Antibody response was assessed using the proxy of IgG secretion and T cell receptor and immunoglobulin framework region recombination was determined by clonality studies. We observed that individuals aged > 60 years demonstrated a higher immune 'age' as calculated by IMMAX score (0.75 compared with 0.48 for individuals aged < 35 years; p = < 0.0001). Immune age negatively correlated with IgG responsivity in older individuals with recent prior exposure to SARS-CoV-2 (b = -0.01; p = 0.05). Higher immune age was also negatively correlated with TCR Vd + Jd receptor diversity regardless of immune challenge (b = -0.02; p = < 0.0001 and b = -0.02; r² = 0.0.35; p = < 0.0001 for control and exposed samples respectively). Our data demonstrate that PBMC samples from older people display a higher cellular immune age and attenuation of immune response. This suggests that future treatments targeting cellular ageing of immune cells may be a useful avenue for investigation to improve immune function in older people.