EXECUTIVE SUMMARY

This evidence-based protocol provides guidance for implementing an age-stratified adult vaccination strategy targeting both infectious disease prevention and potential reduction of chronic disease risk. Recent advances in immunology have revealed multiple mechanisms by which vaccinations may confer protection beyond their primary targets, including trained immunity, reduction of inflammatory burden, and prevention of infection-triggered pathological cascades.

This protocol employs a Bayesian epistemological framework that distinguishes between established direct benefits (Level I), probable off-target effects (Level II-III), and emerging hypotheses (Level IV-V). Recommendations are stratified by age cohort and risk profile, with specific guidance for implementation in clinical practice.

Key recommendations include:

1. Universal annual influenza vaccination with consideration of high-dose/adjuvanted formulations for patients ≥65 years and those with risk factors for cardiovascular disease or cognitive decline
2. Early initiation of recombinant zoster vaccine (Shingrix) at age 50 with consideration for earlier administration in high-risk individuals
3. Pneumococcal conjugate vaccination (PCV20) at age 50 or earlier in patients with cardiometabolic risk factors
4. Annual COVID-19 vaccination with consideration of enhanced scheduling for older adults and high-risk populations
5. RSV vaccination for adults ≥60 years with risk-based consideration for those 50-59 years
6. Completion of Tdap/Td, hepatitis B, and other core vaccines per standard guidance

Implementation should include baseline and follow-up inflammatory biomarker assessment where feasible, integration with lifestyle optimization strategies, and a systematic approach to monitoring for both direct and off-target outcomes.

SECTION I: SCIENTIFIC RATIONALE AND EVIDENCE FRAMEWORK

A. Pathophysiological Basis for Vaccination in Chronic Disease Prevention

Current understanding of chronic disease pathogenesis identifies three key mechanisms through which strategic vaccination may reduce disease burden:

1. Infection-Triggered Pathological Cascades
   • Acute infections can initiate or accelerate pathological processes in multiple organ systems
   • Cardiovascular events demonstrate 3-6 fold increased incidence following respiratory infections
   • Viral and bacterial infections have been linked to accelerated cognitive decline in longitudinal studies
   • Preventing triggering infections may avert downstream pathological cascades
2. Chronic Inflammatory Burden (“Inflammaging”)
   • Low-grade chronic inflammation correlates with accelerated aging and disease progression
   • Cumulative pathogen burden contributes to pro-inflammatory state through multiple pathways
   • Strategic vaccination may mitigate overall inflammatory burden through both direct and indirect effects
3. Trained Immunity Modulation
   • Certain vaccines induce persistent epigenetic and metabolic reprogramming of innate immune cells
   • Enhanced innate immune readiness improves response to diverse pathogens beyond vaccine targets
   • These effects may confer broad protection against infections and potentially modulate chronic disease processes

B. Evidence Classification System