London Longevity Club - Clinical Research Consortium
Background: Accumulating evidence demonstrates that vaccines confer varying degrees of benefits beyond their primary target diseases. A systematic approach to adult vaccination could potentially reduce chronic disease burden while extending healthspan.
Methods: We conducted a comprehensive review of over 2,000 studies examining direct and indirect effects of adult vaccinations. Evidence was evaluated using a Bayesian framework, classifying findings as established (Level I), probable (Level II-III), or speculative (Level IV-V).
Results: We present a comprehensive assessment of all available adult vaccines, organized by biological system and evidence strength. Four vaccines (influenza, pneumococcal, herpes zoster, and Tdap) demonstrate robust evidence for significant off-target benefits, while others show limited or speculative effects. Emerging vaccine technologies targeting cytomegalovirus, Epstein-Barr virus, and senescent cells show promising preclinical results for potential longevity applications.
Conclusions: This update provides an evidence-based framework for clinicians to optimize vaccination strategies across adult age cohorts, with special attention to both established vaccines and emerging technologies with potential healthspan benefits.
Vaccination has traditionally been conceptualized as a strategy for infectious disease prevention. However, robust epidemiological and mechanistic evidence now demonstrates that certain vaccines may confer "off-target" benefits beyond their primary indications. This suggests a novel paradigm wherein strategic vaccination across adulthood could serve as an adjunctive approach to chronic disease prevention and healthspan optimization.
This clinical practice update presents a comprehensive assessment of all available and emerging adult vaccines, evaluating both direct effects and potential off-target benefits for chronic disease prevention and longevity.
We employed a Bayesian epistemological framework to evaluate evidence, classifying findings into confidence levels and distinguishing established effects from emerging hypotheses.
Table 1. Evidence Classification Framework
| Level | Confidence | Source of Evidence | Example |
|---|---|---|---|
| I | High | Multiple RCTs, meta-analyses with narrow CIs | Influenza vaccine reducing CV events (RR=0.70, 95% CI: 0.53-0.85) |
| II | Moderate | Single RCT, well-designed observational studies | Herpes zoster vaccine reducing stroke risk (HR=0.80, 95% CI: 0.67-0.96) |
| III | Moderate-Low | Cohort/case-control studies with methodological limitations | Vaccine associations with reduced dementia incidence |
| IV | Low | Mechanistic/laboratory studies without clinical validation | Epigenetic changes in immune cells post-vaccination |
| V | Very Low | Theoretical mechanisms, expert opinion | Potential metabolic benefits of specific vaccines |
Two primary mechanisms appear to underlie the broader health impacts of vaccination:
1. Trained Immunity: Epigenetic and metabolic reprogramming of innate immune cells, enhancing responses to heterologous pathogens and potentially modifying inflammatory responses to endogenous damage signals. Most robustly demonstrated with BCG vaccine, but also observed with certain adjuvanted vaccines.
2. Reduction of Pathogen-Induced Inflammation: By preventing specific infections, vaccines may avert pathogen-triggered inflammatory cascades that can exacerbate or precipitate chronic conditions.