Exercise and vaccine immune response: A scoping review exploring the underlying immunological mechanisms

The precise mechanisms by which exercise modulates the immune response to vaccination remain largely unelucidated in the existing literature. This scoping review aims to compile and critically analyse the available evidence pertaining to the underlying mechanisms responsible for the enhancing effect of exercise on vaccine-induced immunity.

The study was planned in line with the PRISMA-ScR guidelines. A comprehensive and structured scoping review of the literature was conducted to investigate the effect of exercise on vaccine immune response. Three key electronic databases-PubMed, Web of Science, and Google Scholar-were systematically searched for relevant studies published from January 1, 1990, to June 30, 2025. Strict inclusion and exclusion criteria were established and rigorously applied to the identified studies. Both animal and human studies were included to ensure a broad and comprehensive assessment of all proposed mechanisms.

The initial literature search yielded 4314 study titles, from which 199 papers were identified as potentially relevant and subsequently subjected to abstract-level examination. Following this screening, 38 studies met the predefined inclusion criteria and were incorporated into this review, comprising 26 human studies (68.42%) and 12 animal studies. The publication dates of the included studies ranged from 1999 to 2025. Overall, 14 distinct mechanisms were identified as potential explanations for the observed effect of exercise on vaccine immune response.

The most compelling mechanisms identified in this review for exercise's enhancing effect on vaccine immune response include: upregulated Interleukin-6 (IL-6) expression, enhanced Interferon-gamma (IFN-γ) expression, immune stimulation resulting from myocyte damage, prolonged antibody persistence, and enhanced immune cell metabolic efficiency in physically active individuals. This review highlights the critical need to identify the optimal "golden zone" of exercise intensity and to further elucidate sex-related dimorphisms to maximise clinical efficacy.