Introduction: Vaccines have transformed public health by preventing infectious diseases; beyond this, they may modulate neuroimmune responses. Neuroinflammation, characterized by microglial activation and pro-inflammatory cytokine release, contributes to cognitive decline and neurodegenerative diseases such as Alzheimer’s (AD) and Parkinson’s (PD). Recent studies indicate that vaccination can influence systemic immune responses, which in turn modulate CNS inflammation through the gut–brain axis and peripheral cytokine signaling. Understanding these mechanisms is crucial for developing immunization strategies that confer neurological as well as systemic benefits. This review provides a comprehensive overview of the interplay between vaccination, neuro-immunity, and cognitive health.
Methods: Objectives and Research Questions:
This review aims to evaluate the influence of vaccination on neuroimmune pathways and cognitive outcomes. Specific questions include:
How do vaccines modulate CNS immune responses and microglial activity?
Can vaccination reduce neuroinflammation associated with cognitive decline?
What strategies optimize vaccine-induced neuroprotective effects?
Methods:
A structured narrative review was conducted. Databases searched included PubMed, Scopus, and Web of Science for publications from January 2015 to May 2025. Keywords included “vaccines,” “neuroimmunology,” “neuroinflammation,” “microglia,” and “cognitive decline.” Inclusion criteria comprised peer-reviewed original research or reviews reporting immune mechanisms and CNS outcomes. Exclusion criteria included case reports, editorials, and studies unrelated to human or relevant animal models. Data extraction focused on vaccine type, immune modulation, CNS biomarkers, and clinical or experimental cognitive outcomes. Studies were categorized into (1) immune mechanisms, (2) neuroinflammation modulation, and (3) cognitive implications. Quality assessment prioritized methodological rigor and reproducibility.
Results: Immune modulation by vaccines: Vaccines stimulate both innate and adaptive immune responses, influencing cytokine profiles and T-cell activation. Peripheral immune modulation can affect microglial phenotypes and CNS homeostasis.
Neuroinflammation and cognitive health: Evidence indicates that influenza and other routine vaccines can reduce chronic neuroinflammatory markers, potentially lowering the risk of AD and PD. Animal studies demonstrate attenuated microglial activation following immunization.
Strategies for optimization: Adjuvant selection, vaccination timing, and booster schedules can enhance neuroprotective benefits. Emerging approaches include designing vaccines that specifically targetCNS-related antigens or modulate systemic inflammation indirectly.
Overall, studies support a potential role for vaccination in maintaining cognitive health, though evidence remains preliminary and heterogeneous.
Conclusion: Vaccination may confer benefits beyond infection prevention, modulating neuroimmune pathways and attenuating chronic neuroinflammation. The CNS effects are mediated through peripheral cytokines, microglial regulation, and systemic immune priming. Limitations include small sample sizes, variability in human immune responses, and scarcity of longitudinal studies. Future research should integrate multi-omics, neuroimaging, and longitudinal cognitive assessments to elucidate mechanisms and optimize vaccination strategies for neuroprotection. Equitable access and population-specific studies are also critical.
Vaccination influences neuroimmune mechanisms with potential implications for reducing neuroinflammation and preserving cognitive function. Optimizing vaccine design, adjuvants, and schedules may enhance CNS benefits. While current evidence is promising, further longitudinal and mechanistic studies are needed to establish causality and maximize neuroprotective effects. Vaccination may thus represent a dual-purpose intervention, protecting both systemic and neurological health.