British researchers analyzed electronic health record data and found that vaccination against respiratory syncytial virus with the AS01 adjuvant was associated with a reduced risk of dementia over the subsequent 18 months. A similar association was previously shown for the shingles vaccine with a similar adjuvant, which may indicate its independent role in preventing dementia. The report is 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. However, in studies where an analysis was conducted by type of drug, the risk reduction was much more pronounced with the recombinant vaccine with the AS01 adjuvant compared to the live attenuated vaccine. This can be explained by two non-mutually exclusive hypotheses: that the risk reduction is associated with a 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 with two immunostimulants - 3-O-desacyl-4'-monophosphoryl lipid A (MPL) and saponin QS-21 - and is also contained 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 had received only the RSV/AS01 vaccine, nearly 104,000 (mean age 69.2 years; 54.9 percent women) who had received only the VZV/AS01 vaccine, and nearly 79,000 (mean age 72-48 years; 57.8 percent women) who had received both vaccines. Each was then randomly matched 1:1 with people who had received the flu vaccine without AS01 but not the RSV or shingles vaccines as controls. Risks were estimated based on the ratio of the limited median survival time (RMTL) to dementia diagnosis in the study and control groups.
It turned out that the risk of dementia diagnosis within 18 months from vaccination was significantly lower with the use of vaccines with AS01: with vaccination against RSV only, 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 percent 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. There was also no significant effect of gender on risk reduction (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 such a connection remain unclear, but the time of onset of the supposed preventive effect and its presence during vaccination against viruses with different potential roles in the pathogenesis of dementia indicate a probable direct contribution of the adjuvant to its development. The authors of the work name stimulation of toll-like receptors 4 (TLR4) and production of interferon gamma (IFNγ) as possible molecular biological mechanisms of the preventive effect of AS01 in the pathogenesis of dementia. Further mechanistic and clinical studies are needed to clarify the potential of AS01 in the prevention of dementia.
Previously, American researchers analyzed data from biobanks in Finland and the UK and discovered many 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.
