The relationship between immunological age determined by Immune Age Index (IMMAX) and response to vaccination against SARS-CoV-2

Immunosenescence contributes to reduced vaccine efficacy in aging populations, but chronological age is an imperfect proxy for the underlying immunological decline. We investigated whether the Immune Age Index (IMMAX), a validated surrogate for the IMM-AGE metric, better predicts vaccination outcomes than chronological age. Using the unique setting of primary SARS-CoV-2 vaccination in immunologically naive individuals, we analyzed anti-spike RBD antibody titers and IMMAX in 658 fully vaccinated adults, including a subgroup of 91 professional firefighters. Both chronological age and IMMAX negatively correlated with antibody titers. Notably, women exhibited IMMAX values matching those of men roughly eight years younger and correspondingly showed higher antibody responses across the entire age range, indicating a sex-based immunological advantage independent of age. In the subgroup of 353 participants vaccinated twice with BNT162b2, our analysis revealed that while antibody titers declined linearly with chronological age, they remained stable across a range of lower IMMAX values before declining beyond an equivalent-years-of-life value of about 60. Professional firefighters displayed significantly lower IMMAX scores than age-, sex-, and lifestyle-matched controls, corresponding to an immune age advantage of 8.24 years. More importantly, they also showed significantly higher antibody titers compared to matched controls. These findings establish IMMAX as a robust, readily measurable biomarker that captures individual variation in immune competence beyond chronological age.