Herpes zoster vaccination and healthy aging: Study connect the dots

In a recent article published in Npj Vaccines, researchers describe how vaccination with recombinant zoster vaccine (RZV) could help prevent Herpes Zoster (HZ) infection (or shingles) and support healthy aging.

Study: Healthy ageing: Herpes zoster infection and the role of zoster vaccination. Image Credit: BaLL LunLa/Shutterstock.com

Background

Reactivation of the varicella-zoster virus (VZV) due to declining immunity causes HZ, a disease condition with several complications, such as hearing impairment, vision loss, and increased risk of stroke and heart attack, i.e., prolonged morbidities and overall poor quality of life. 

In the United States (US) alone, over one million cases of HZ are reported annually, with numbers higher in females than males. Vaccines, such as RZV, can help prevent HZ and its complications.

It is much needed as population aging is a demographic trend worldwide that has increased healthcare costs and the risk of infectious diseases.

Herpes Zoster prevention and management

Currently, two vaccines for HZ are available: the Zoster Vaccine Live (ZVL) and RZV. 

ZVL, an attenuated form of VZV, also known as vOka, is administered as a single dose and confers protection against both chickenpox and shingles.

Even though it is more potent against shingles, the limitation of ZVL is that it is ineffective in individuals with primary or acquired immunodeficiency.

RZV's efficacy, safety, and acceptability

RZV, on the other hand, is a two-dose vaccine that combines glycoprotein E or gE from the VZV virus with AS01B, an adjuvant system that helps to improve the immune response to the vaccine, especially in older adults.

Its component, 3-O-desacyl-4'-monophosphoryl lipid A (MPL), activates Toll-like receptor 4 (TLR4), which helps to enhance the immune response, whereas its other component, QS-21, stimulates the immune system.

Typically, its second dose is administered two to six months after the first dose; however, a shorter vaccine schedule (short by one to two months), may also be followed for immunodeficient or immunosuppressed individuals. Compared to ZVL, RZV produces a more robust immune response and higher levels of interleukin 2.

Two trials, ZOE-50 and ZOE-70, estimated RZV efficacy at different time points and found efficacy equivalent to 84.2%, 72.7%, and 73.2% for years 8, 9, and 10 post-vaccinations, evidencing its long-lasting effects. Data collection for evaluating RZV efficacy beyond ten years is ongoing.

RSV worked equally well with people of different ages, genders, and ethnicities. It was also effective in patients with common medical conditions like hypertension and diabetes. 

The decline in immune function that occurs with aging is known as immunosenescence. Notably, RZV overcame the immunosenescence of those aged 80 years and above. A post-hoc analysis of multiple studies revealed that RZV was above 90% effective even in pre-frail and frail individuals.

RZV's phase III trials among immunocompromised adults were successful, implying it conferred protection to those with weakened immune systems.

Studies have revealed that HZ is associated with severe pain in the majority of patients, with 15.8% of patients reporting the worst pain imaginable in a study.

Increased HZ-related pain worsens the quality of life and physical functioning of shingles patients, especially when accompanied by other discomforts, such as itching and allodynia.

Another notable complication of herpes zoster is persistent pain in the area affected by the rash, known as postherpetic neuralgia (PHN). HZ and PHN also result in higher healthcare costs and productivity losses, with a mean of 9.5 consultations for PHN patients and hospitalization needed for up to 4% of HZ patients. RZV reduces the occurrence of HZ and confers protection against PHN. 

RZV is generally safe, with adverse reactions of only mild to moderate intensity, lasting for not more than three days. Thus, people received its second dose ~95% in clinical trials and ~70%-80% in real-world studies. Apart from these reactions, it was as safe as a placebo, irrespective of age, gender, or race.

However, a case analysis revealed that after six weeks of RZV administration, the risk for Guillain-Barré syndrome, a rare neurological disorder, was increased slightly. 

Given its overall benefit and lack of evidence to establish causality, RZV vaccination is still highly favored. Furthermore, the RZV's safety profile remains clinically acceptable ten years after vaccination.

Data from the ZOE-70 study showed that RZV significantly reduced the use of pain medication in individuals with confirmed HZ.

In addition to preventing HZ episodes and the associated pain, RZV also reduced the severity of pain in individuals who experienced HZ despite vaccination (breakthrough infection). Importantly, RZV reduced the burden of HZ pain by more than 90% in adults aged ≥50 years.  

Modeling studies using mathematical models to simulate real-world scenarios predict that RZV has the potential to reduce hospitalizations, outpatient visits, and general practitioner visits related to HZ, implying vaccination could reduce the number of people seeking medical care for HZ.

It also implies that RZV receipt could reduce work losses due to HZ. Furthermore, a review of multiple studies suggests that RZV is more cost-effective than ZVL.

A modeling study done in Germany found that the number needed to vaccinate (NNV) with RZV to prevent one case of shingles and PHN was between six and 10 and 38 and 48, respectively.

The NNV to prevent an HZ case was lower in individuals aged 50-69 than 70 years and older, suggesting that vaccinating younger individuals with RZV may have a greater public health impact for preventing shingles.

Regarding acceptability, Canada and the UK have preferential recommendations for RZV, given its higher efficacy, longer duration of protection, and cost-effectiveness. 

Other factors, such as public funding and considerations for use in immunocompromised individuals, may also lead to varying recommendations for RZV across countries.

Conclusions

The study critically evaluated worldwide HZ prevalence to inform future strategies for shingles prevention and management.

The incidence of vaccine-preventable infectious diseases, such as HZ, is now higher in adults rather than children. Thus, the need of the hour is adult vaccination programs, including against HZ, to reduce morbidity in older adults, maintain quality of life, and provide socioeconomic benefits. 

Adult vaccination is also crucial for healthy aging, i.e., not just adding years to life but enhancing quality years. However, achieving this goal requires the requisite infrastructure to facilitate high vaccination coverage. 

Some recent reports suggest that RZV vaccination may decrease the risk of dementia based on analyses of retrospective data from vaccinated and unvaccinated individuals.

Further research is needed to understand the underlying mechanisms behind the association between HZ vaccination and dementia and establish a causal relationship. 

Written by

Neha Mathur

Neha is a digital marketing professional based in Gurugram, India. She has a Master’s degree from the University of Rajasthan with a specialization in Biotechnology in 2008. She has experience in pre-clinical research as part of her research project in The Department of Toxicology at the prestigious Central Drug Research Institute (CDRI), Lucknow, India. She also holds a certification in C++ programming.