A recent study evaluated the impact of age, sex, prior SARS-CoV-2 infection, and cytomegalovirus (CMV) serostatus on humoral and T-cell responses following a fourth dose of the bivalent BNT162b2 vaccine. In a cohort of 41 adults, researchers found that anti-RBD IgG titres increased significantly across all participants, indicating a robust humoral response that was largely independent of age or prior infection history. However, the cellular immune response exhibited notable heterogeneity, particularly among older adults and males, who demonstrated reduced frequencies of IFN-γ–producing CD4+ T cells post-vaccination.

The study highlights the complex interplay between immunosenescence and vaccine responsiveness. While the booster dose effectively enhanced overall humoral immunity, the quality of cellular responses varied significantly based on demographic factors. Specifically, older adults and those with prior SARS-CoV-2 infections showed diminished CD4+ recall responses, while infection-naïve and female participants exhibited stronger gains. Additionally, markers of CMV-related immune remodelling were linked to reduced IFN-γ responses, suggesting that chronic CMV infection may hinder effective antiviral immunity even in mid-adulthood.

These findings underscore the necessity of evaluating both humoral and cellular immunity in vaccination strategies, particularly in older populations. The study suggests that incorporating immune-ageing markers into vaccination protocols could enhance booster efficacy, potentially leading to more tailored and effective vaccination strategies for aging populations. This approach may shift current research paradigms by emphasizing the importance of understanding individual immune profiles in the context of vaccine responses.

Source: academic.oup.com