Over the past decade, numerious herpes zoster cases were prevented with two doses of a U.S. FDA-approved vaccine that contains an adjuvant. According to new research, there may be an additional, measurable benefit from vaccination.
A Brief Communication published by NPJ Vaccines on June 25, 2025, reported a lower risk of dementia associated with AS01-adjuvanted vaccination against shingles.
In propensity-score matched cohort studies involving 436,788 individuals, both the AS01-adjuvanted shingles and respiratory syncytial virus vaccines, administered individually or in combination, were associated with a reduced risk of dementia at 18 months.
AS01 may protect against dementia through specific immunological pathways.
In particular, stimulation of toll-like receptor 4 with monophosphoryl lipid A (MPL; one of the components of the AS01 system) has been shown to improve Alzheimer’s disease pathology in mice.
In addition, the two main ingredients of AS01, MPL and QS-21 (a purified plant extract derived from Quillaja saponaria), act synergistically to activate macrophages and dendritic cells, triggering an age-independent cytokine cascade that culminates in the production of interferon gamma (IFN-γ).
IFN-γ might attenuate amyloid plaque deposition (as seen in mice) and is negatively correlated with cognitive decline in cognitively unimpaired older adults.
These neuroprotective mechanisms may reach their full potential at or below the dose of AS01 administered within a single vaccine, so that administering both the AS01 shingles and RSV vaccines does not provide any additional benefits.
This saturation effect could also explain why the level of protection against dementia appears similar between the AS01 shingles vaccine (which is given in two doses) and the AS01 RSV vaccine (administered as a single dose).
No difference was observed between the two AS01-adjuvanted vaccines, suggesting that the AS01 adjuvant itself plays a direct role in reducing the risk of dementia.
A previous study found similar cross-protection benefits.
In July 2024, a University of Oxford-led study concluded that receiving the recombinant Shingrix® vaccine was associated with a 17% increase in diagnosis-free time, translating into 164 additional days lived without a diagnosis of dementia in those subsequently affected.
As of July 7, 2025, shingles vaccination services are offered at most pharmacies in the United States.