British researchers analyzed electronic medical record data and found that vaccination against respiratory syncytial virus (RSV) with the AS01 adjuvant was associated with a reduced risk of dementia over the subsequent 18 months. A similar association was previously demonstrated for the shingles vaccine with a similar adjuvant, suggesting that it may play an independent role in preventing dementia. The report was published in the journal npj Vaccines.
Various studies have repeatedly shown that vaccination against the varicella-zoster virus, which causes chickenpox and shingles, is associated with a reduced risk of dementia, and this association is most likely causal. Moreover, in studies that analyzed vaccine types, the risk reduction was significantly more pronounced with the recombinant AS01-adjuvanted vaccine compared to the live-attenuated vaccine. This may be explained by two non-mutually exclusive hypotheses: that the reduced risk is related to the higher efficacy of the adjuvanted vaccine in preventing herpes (it is indeed higher), and that the adjuvant itself may have a preventive effect. This adjuvant, AS01, is a liposome containing two immunostimulants, 3-O-desacyl-4'-monophosphoryl lipid A (MPL) and saponin QS-21, and is also found in some other vaccines.
To test the second hypothesis, Paul Harrison and colleagues at the University of Oxford analyzed electronic health record data from nearly 36,000 people (mean age 72.8 years; 58.1 percent women) who received only the respiratory syncytial virus (RSV) vaccine with AS01, nearly 104,000 (mean age 69.2 years; 54.9 percent women) who received only the varicella-zoster virus (VZV) vaccine with AS01, and nearly 79,000 (mean age 72.48 years; 57.8 percent women) who received both vaccines. Each of these people was then randomly matched in a 1:1 ratio with people who had received the flu vaccine without AS01, but not the RSV or shingles vaccines, as a control group. Risks were estimated based on the ratio of the limited median survival time (RMTL) to dementia diagnosis in the study and control groups.
It was found that the risk of being diagnosed with dementia within 18 months after vaccination was significantly lower with the use of vaccines containing AS01: with vaccination against RSV only, the RMTL was 0.71 (p = 0.000028), against VZV only - 0.82 (p = 0.00027), and with both vaccinations - 0.63 (p = 4.7 × 10−12). This corresponds to 29, 18, and 37% additional time without a dementia diagnosis, or 87, 53, and 113 days over 18 months, respectively. The risk of dementia did not differ statistically significantly between those who received only the RSV vaccine and those who received both. No significant effect of gender on risk reduction was also observed (p = 0.40, 0.46, and 0.14, respectively). Similar patterns were found when analyzing the risk of the combined outcome of dementia or death.
The mechanisms of this association remain unclear, but the timing of the onset of the putative preventive effect and its presence during vaccination against viruses with different potential roles in the pathogenesis of dementia indicate a likely direct contribution of the adjuvant to its development. The authors of the study suggest stimulation of toll-like receptors 4 (TLR4) and interferon gamma (IFNγ) production as possible molecular biological mechanisms of AS01's preventive effect in the pathogenesis of dementia. Further mechanistic and clinical studies are needed to elucidate the potential of AS01 in dementia prevention.
Previously, American researchers analyzed data from biobanks in Finland and the UK and discovered numerous correlations between chronic viral infections and the development of neurodegenerative diseases—Alzheimer's and Parkinson's diseases, amyotrophic lateral sclerosis, multiple sclerosis, and various dementias.
