In a recent study published in Nature Medicine, researchers investigated the effects of recombinant shingles vaccines on dementia.

​​​​​​​Study: The recombinant shingles vaccine is associated with lower risk of dementia. Image Credit: Gorodenkoff/Shutterstock.com

Background

Varicella-zoster virus (VZV), or human herpesvirus 3, causes varicella (chickenpox) and shingles. Given the potential for adverse repercussions from shingles, health authorities in several nations advise immunization for older individuals.

Recent research suggests 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Existing data is sparse and solely applies to live herpes zoster vaccine withdrawn in the United States (US) and other countries; therefore, the efficacy of the recombinant shingles vaccine remains uncertain.

About the study

In the present observational study, researchers investigated whether the recombinant shingles vaccine could lower dementia risk. 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 generated by the swift uptake of recombinant vaccines and the concomitant disuse of live vaccines from October 2017 onward.

They compared individuals who received shingles vaccination right after vs. right before the step change to determine the associations between recombinant vaccine exposure and subsequent dementia incidence.

The researchers performed propensity score-type matching (PSM) to adjust for variations in vaccinated population characteristics. They matched 103,837 people receiving the initial shingles vaccination in the November 2017-October 2020 period (95% recombinant vaccine recipients; median follow-up, 4.2 years) to an equivalent number of individuals receiving their initial vaccination in the October 2014-September 2017 period (98% live vaccine recipients; median follow-up, 6.0 years).

The researchers determined restricted mean time lost (RMTL) and hazard ratios (HR) for analysis. They aligned cohort-level follow-up horizons (primary analysis) with matched individual pair-level (coarsened exact matching analysis) as additional analysis.

They also investigated gender-based differences in the associations. They compared the results obtained by restricting analyses to predominant vaccine recipients, limiting exposure windows to six months on both sides of the step change, and excluding recipients of both vaccines with socioeconomic deprivation adjustments.

Results

Compared to live vaccine recipients, individuals predominantly receiving the recombinant herpes zoster vaccine showed lower dementia development risk in the following six years (RMTL ratio of 0.8), indicating 17% more diagnosis-free time or 164 additional days without dementia diagnosis among affected individuals.

The relationship was consistent across dementia subtypes except for Lewy body and frontotemporal dementia.

In addition, individuals vaccinated after October 2017 showed a significantly lower likelihood of developing herpes zoster infections in the six years post-vaccination, with an RMTL ratio of 0.7.

Controlling for socioeconomic deprivation and restricting analyses to predominant vaccine recipients, exposure periods to six months of step change sides, and excluding recipients of both vaccines yielded similar findings.

Further, the researchers found similar risk differences, limiting follow-up to the period before the coronavirus disease in 2019 (COVID-19, HR, 0.7).

They found similar results when comparing the primary analyses and coarsening exact-type matching for covariates such as age, race, biological sex, and neurological disorders using bootstrap or parametric variance estimates.

The recombinant herpes zoster vaccine was also related to lower dementia risks than Tdap and influenza vaccines (RMTL ratios between 0.7 and 0.9).

The association was found in males and females but was higher among females than males (22% vs. 13% more diagnosis-free time lived). The team observed associations with shingles in men and women without gender moderation.

The mechanisms behind the putative dementia protection provided by shingles vaccinations remain unknown. One probable explanation is that it protects against herpes infection, which causes dementia. This concept has been discussed for decades and may explain dementia risk reductions from both types of herpes zoster vaccinations.

The recombinant vaccination provides better protection, with effectiveness diminishing with time. The recombinant vaccination contains immunostimulants, which may contribute to dementia risk. The observed HR values at the end of follow-up may imply that the vaccination delays dementia onset; however, this is not well supported and requires replication.

Conclusions

The study showed that recombinant shingles vaccinations 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 decreased dementia risk. The finding provides the results’ credibility and has crucial public health implications.

The recombinant shingles vaccination had a 9.0% stronger protective impact in females than in males, unrelated to women’s superior shingles protection.

This finding calls for more exploration and large-scale randomized controlled studies to confirm the vaccine’s possible further benefits. Further research should include non-observational designs to assess the causation of the correlations.