Skeletal muscle as a dynamic immunological niche for vaccination.

Intramuscular vaccination has long been a cornerstone of preventive medicine and has substantially reduced global mortality from infectious disease. As vaccine development has expanded to address increasingly complex targets, including chronic infections and cancer, it has become clear that vaccine efficacy depends not only on antigen design but also on the inflammatory and cellular cues present at the site of delivery. Despite this, the skeletal muscle-the most common site of vaccine administration-has received comparatively little attention as an immunological environment. Skeletal muscle is a highly dynamic, regenerative tissue whose immune composition is actively remodeled by injury, aging, and disease. How these context-dependent immune states shape vaccine uptake and downstream immune responses remains poorly understood. In this review, we examine the immune landscape of skeletal muscle in health and disease and discuss how its intrinsic regenerative programs, and their disruption in conditions such as sarcopenia, may influence intramuscular vaccine responses.