UK: Researchers at the University of Oxford have found in a new study that older U.S. adults who received AS01-adjuvanted vaccines—either for shingles or respiratory syncytial virus (RSV)—were less likely to be diagnosed with dementia within 18 months. Since both vaccines showed comparable results, the study points to the AS01 adjuvant as a potential contributor to the protective effect against dementia.
Published in npj Vaccines, the large-scale study assessed over 430,000 individuals using electronic health record (EHR) data from the U.S.-based TriNetX network. It compared those who received AS01-based shingles (Shingrix) or RSV (Arexvy) vaccines with individuals who received flu vaccines but not the AS01-adjuvanted shots.
The findings were as follows:
- Individuals who received either the AS01 shingles or RSV vaccine had a significantly lower risk of developing dementia.
- Recipients of the RSV vaccine experienced a 29% longer dementia-free period over 18 months.
- Those who received the shingles vaccine had an 18% longer duration without a dementia diagnosis.
- Participants who received both vaccines showed the greatest benefit, with a 37% increase in dementia-free time compared to flu vaccine recipients.
- There was no significant difference in dementia risk reduction between the shingles and RSV vaccines.
- Receiving both AS01 vaccines did not provide additional benefits, suggesting the AS01 adjuvant may drive the observed protective effect.
- The protective association was consistent across both men and women.
- The findings remained valid even when early dementia diagnoses (within three months of vaccination) were included.
AS01 is composed of monophosphoryl lipid A (MPL) and QS-21, substances that stimulate specific immune pathways. Prior research in animal models suggests that MPL may mitigate Alzheimer's-related changes in the brain, and both MPL and QS-21 activate immune cells and boost the production of interferon-gamma, a molecule linked to slower cognitive decline.
Although the exact biological mechanism remains uncertain, the researchers noted that the protective effect seems unlikely to be solely due to infection prevention since the observed benefits emerged within months of vaccination, too soon for infection avoidance alone to account for the dementia risk reduction.
The findings are based on retrospective observational data, and while the study adjusted for various confounding factors, the authors acknowledged limitations such as potential misclassification of vaccine brands and lack of socioeconomic data. Nevertheless, the consistent patterns across different analyses support the need for further exploration.
“Our data suggest that vaccines containing the AS01 adjuvant might offer benefits beyond infection prevention,” the authors stated. “Further clinical trials and mechanistic research are essential to confirm these effects and understand how long the protection might last.”
They conclude, "If confirmed, these findings could shape future strategies to delay or prevent dementia—one of the world’s leading causes of disability in older adults—using existing vaccination platforms."
Reference:
Taquet, M., Todd, J. A., & Harrison, P. J. (2025). Lower risk of dementia with AS01-adjuvanted vaccination against shingles and respiratory syncytial virus infections. Npj Vaccines, 10(1), 1-6. https://doi.org/10.1038/s41541-025-01172-3
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