Off-Target Effects of Recombinant Zoster Vaccine: Clinical Benefits, AS01B Adjuvant Immunobiology, and Observational Evidence

Background/Objectives: The recombinant zoster vaccine (RZV), Shingrix®, has shown great efficacy in protecting against herpes zoster. However, emerging evidence suggests that this RZV might provide benefits that extend beyond preventing varicella zoster virus (VZV) reactivation. Specifically, this scoping review explored the literature to investigate the reported non-zoster, off-target effects of the Shingrix® RZV, and the possible mechanistic explanations for these effects. Methods: Keyword searches of PubMed database were conducted, along with manual searches of other relevant journals and reference lists of primary articles. Results: Evidence from the included studies demonstrated relationships between administration of RZV vaccination and reduced risk of dementia, Alzheimer’s disease and major adverse cardiological events (MACEs), while also conferring geroprotective effects. Mechanistic studies identified two possible causes, namely VZV suppression and AS01B adjuvant immunoregulation. Prevention of herpes zoster resulted in reduced risk of associated cognitive impairment and vasculopathy, reducing incidence of dementia and MACE. AS01B adjuvant was also linked to persistent monocyte reprogramming, and enhanced innate immune response and memory, known as “trained immunity”, which provided a plausible explanation for the observed off-target effects. Adverse events because of RZV administration were rare but included Guillain–Barré syndrome (GBS), autoimmune encephalitis and autoimmune flares occurring after vaccination. However, there is insufficient evidence to indicate a causal relationship between RZV administration and these rare immune-mediated adverse effects, and post-marketing surveillance still support a favourable safety profile. Conclusions: Current evidence suggests that RZV administration confers numerous off-target benefits via VZV suppression and the immunomodulatory effects of the AS01B adjuvant. As clinical evidence remains observational, further investigation of the pleiotropic effects of RZV should be carried out to explore its role in reducing all-cause mortality.