In a recent study published in Nature Medicineresearchers investigated the effects of recombinant herpes zoster vaccines on dementia.
Study: Recombinant shingles vaccine associated with lower risk of dementia. Image credit: Gorodenkoff/Shutterstock.com
Record
The varicella-zoster virus (VZV), or human herpesvirus 3, causes varicella (chicken pox) and shingles. Given the potential for adverse effects from shingles, health authorities in many nations advise vaccination for older individuals.
Recent research shows that the live herpes zoster (shingles) vaccination may protect against dementia. Most studies comparing vaccinated and unvaccinated groups are susceptible to selection and healthy vaccine biases.
Existing data are sparse and apply only to the live zoster vaccine that was withdrawn in the United States (US) and other countries. Therefore, the efficacy of the recombinant zoster vaccine remains uncertain.
About the study
In the present observational study, researchers investigated whether the recombinant shingles vaccine could reduce the risk of dementia. They also compared the risk of dementia among shingles, influenza, and tetanus/diphtheria/pertussis (Tdap) vaccine recipients.
The researchers used electronic medical records and a US-based natural experimental opportunity created by the rapid uptake of recombinant vaccines and the concomitant disuse of live vaccines from October 2017 onwards.
They compared subjects who received shingles vaccination immediately after versus immediately before the step change to determine associations between exposure to the recombinant vaccine and the subsequent incidence of dementia.
The researchers performed propensity score matching (PSM) to adjust for variations in the characteristics of the vaccinated population. They matched 103,837 people who received their primary vaccination against zoster in November 2017–October 2020 (95% recipients of recombinant vaccine, median follow-up, 4.2 years) with an equivalent number of people who received their primary vaccination in October 2014–September 2014 (98% live vaccine recipients, median follow-up, 6.0 years).
Investigators determined restricted mean time lost (RMTL) and hazard ratios (HR) for analysis. They aligned follow-up horizons at the cohort level (primary analysis) with matched individual pair level (exact match analysis) as an additional analysis.
They also investigated gender-based differences in associations. They compared the results obtained by restricting analyzes to dominant vaccine recipients, limiting exposure windows to six months on either side of the stage change, and excluding recipients of both vaccines with adjustments for socioeconomic deprivation.
Results
Compared with live vaccine recipients, subjects who received primarily the recombinant zoster vaccine had a lower risk of developing dementia over the next six years (RMTL ratio 0.8), indicating 17% more time without a diagnosis, or 164 additional days without a diagnosis of dementia among affected individuals.
The relationship was consistent across all dementia subtypes except Lewy body and frontotemporal dementia.
In addition, people vaccinated after October 2017 showed a significantly lower probability of developing shingles infections at six years after vaccination, with an RMTL ratio of 0.7.
Controlling for socioeconomic deprivation and restricting analyzes to dominant vaccine recipients, six-month cross-stage exposure periods, and excluding recipients of both vaccines yielded similar findings.
In addition, the researchers found similar risk differences, restricting follow-up to the period before the 2019 coronavirus disease (COVID-19, HR, 0.7).
They found similar results when comparing primary analyzes and crude exact-type matching for covariates such as age, race, biological sex, and neurological disorders using bootstrapped or parametric variance estimates.
Recombinant zoster vaccine was also associated with lower risks of dementia than Tdap and influenza vaccines (RMTL ratios between 0.7 and 0.9).
The association was found in both men and women, but was higher among women than men (22% vs. 13% longer time without diagnosis). The team observed associations with shingles in men and women without adjusting for sex.
The mechanisms behind the supposed protection against dementia provided by shingles vaccinations remain unknown. One possible explanation is that it protects against herpes infection, which causes dementia. This concept has been debated for decades and may explain the reduction in dementia risk from both types of shingles vaccinations.
Recombinant vaccination provides better protection, with effectiveness decreasing over time. The recombinant vaccine contains immunostimulants, which may contribute to the risk of dementia. The observed HR values at the end of follow-up may suggest that vaccination delays the onset of dementia. However, this is not well supported and requires replication.
conclusions
The study showed that recombinant zoster vaccines had a reduced incidence of dementia compared to live vaccines within six years.
This translates to a 17% increase in time without a dementia diagnosis, a huge effect size, especially given that live shingles vaccinations are also associated with a reduced risk of dementia. The finding provides credibility to the results and has critical implications for public health.
Recombinant zoster vaccination had a 9.0% stronger protective effect in women than in men, unrelated to superior zoster protection in women.
This finding requires more exploration and large-scale randomized controlled trials to confirm potential further benefits of the vaccine. Further research should include non-observational designs to assess causality of associations.
