Preventing herpes zoster through vaccination: New developments

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FIGURE 1. Rates of vaccination against herpes zoster in adults age 60 and older between 2007 and 2013.

Although the vaccine has been recommended since 2008, uptake has been slow. Figure 1 shows the rate of HZ vaccination in adults age 60 and older surveyed in the National Health Interview Survey from 2007 to 2013.35 Eight years after the vaccine was licensed, only 28% of eligible patients had been vaccinated. Assuming the current rate of increase remains constant, it will take 7 more years to reach a 60% coverage rate—the same as for pneumococcal vaccine36—and 18 years to reach universal coverage.

Barriers to vaccination

Several barriers to HZ vaccination might account for the slow uptake.

For the first few years the vaccine was available, the requirement to store it frozen presented an obstacle for some physicians.37 Physicians may also have been discouraged by the cumbersome Medicare reimbursement process because while the administration fee is covered through Medicare Part B, the live­-attenuated vaccine is reimbursed only through Medicare Part D, a benefit that varies by plans. Other barriers to physicians are supply shortages, high up-front costs, and uncertainties regarding the duration of vaccine protection, its safety, and side effects.38–40

Patient barriers include lack of physician recommendation, lack of familiarity with the vaccine, high out-of-pocket costs, the perception that they are at low risk for HZ, underestimation of the pain associated with HZ and postherpetic neuralgia, and fear of vaccine adverse effects.39,41,42

Interventions to increase vaccination rates

Certain interventions have been shown to increase vaccination adherence in general and HZ vaccination in particular. In randomized trials involving other vaccines, electronic medical record reminders supporting panel management or nurse-initiated protocols have been proven to increase vaccination rates, but these methods have not been tested for HZ vaccine specifically.43,44

In an observational study, Chaudhry et al found that the number of HZ vaccinations administered at the Mayo Clinic increased 43% in one practice and 54% in another after the implementation of an electronic alert.45 A randomized controlled trial showed that an informational package discussing HZ and the vaccine sent to patients via either their electronic personal health record or traditional mail increased HZ vaccination by almost 3 times.46

Pharmacists can also influence vaccination rates. States that provide full immunization privileges to pharmacists have vaccination rates significantly higher than states with restricted or no authorization.47


Unlike the Centers for Medicare and Medicaid Services, the ACIP does consider cost-effectiveness in their vaccine recommendations. Because of the morbidity associated with HZ and postherpetic neuralgia as well as the economic impact, vaccination is generally considered cost-effective for adults age 60 and older.48,49

Analyses have demonstrated that cost-effectiveness hinges on 4 factors: initial vaccine efficacy, the duration of efficacy, the age-specific incidence of HZ, and the cost of the vaccine.

For patients ages 50 to 59, the incidence of HZ is low, and because the duration of vaccine efficacy is short even though initial vaccine efficacy is high, vaccination in this age group offers poor value.50 At older ages, the incidence of HZ and postherpetic neuralgia rises, making vaccination more cost-effective. After age 60, the vaccine is cost-effective at all ages, although age 70 appears to offer the optimal trade-off between increasing incidence and declining vaccine efficacy.48,49

For patients who plan to be vaccinated only once, waiting until age 70 would appear to offer the best value.51 For those who are willing to receive a booster dose, the optimal age for vaccination is unknown, but will likely depend on the effectiveness, cost, and duration of the booster.


In 2015, GlaxoSmithKline tested a new HZ vaccine containing a single VZV glycoprotein in an AS01B adjuvant system (HZ/su vaccine).52 In a phase 3 randomized trial involving 15,411 immunocompetent persons age 50 and older, a 2-dose schedule of HZ/su vaccine was 97% effective in preventing HZ (Table 1).53 Importantly, the vaccine was equally effective in older patients.

This vaccine also had a high rate of adverse reactions, with 17% of vaccine recipients vs 3% of placebo recipients reporting events that prevented normal everyday activities for at least 1 day. However, the rate of serious adverse reactions was the same in both groups (9%). The company announced that they intended to submit a regulatory application for HZ/su vaccine in the second half of 2016.54

Because of its high efficacy, HZ/su vaccine has the potential to change practice, but several issues must be resolved before it can supplant the current vaccine.

First, the AS01B adjuvant is not currently licensed in the United States, so it is unclear if the HZ/su vaccine can get FDA approval.52,55

Second, there are several questions about the efficacy of the vaccine, including long-term efficacy, efficacy in the elderly, and efficacy in the case of a patient receiving only 1 of the 2 required doses.

Third, the impact of HZ/su vaccine on complications such as postherpetic neuralgia has not been established. The clinical trial (NCT01165229) examining vaccine efficacy against postherpetic neuralgia incidence and other complications in adults age 70 and older has recently been completed and data should be available soon. Given the extremely high efficacy against HZ, it is likely that it will be close to 100% effective against this complication.

Fourth, there is uncertainty as to how the HZ/su vaccine should be used in patients who have already received the live-attenuated vaccine, if it is determined that a booster is necessary.

Finally, the vaccine is not yet priced. Given its superior effectiveness, particularly in older individuals, competitive pricing could dramatically affect the market. How Medicare or other insurers cover the new vaccine will likely influence its acceptance.


Immunocompromised patients are at highest risk for developing HZ. Unfortunately, there are currently no HZ vaccines approved for use in this population. The current live-attenuated vaccine has been demonstrated to be safe, well tolerated, and immunogenic in patients age 60 and older who are receiving chronic or maintenance low to moderate doses of corticosteroids.56

A clinical trial is being conducted to assess the immunogenicity, clinical effectiveness, and safety of the vaccine in rheumatoid arthritis patients receiving antitumor necrosis factor therapy (NCT01967316). Other trials are examining vaccine efficacy and safety in patients with solid organ tumors prior to chemotherapy (NCT02444936) and in patients who will be undergoing living donor kidney transplantation (NCT00940940). Researchers are also investigating the possibility of vaccinating allogeneic stem cell donors before donation in order to protect transplant recipients against HZ (NCT01573182).

ZVHT and HZ/su vaccination in immunocompromised patients

Heat-treated varicella-zoster vaccine (ZVHT) is a potential alternative for immunocompromised patients. A 4-dose regimen has been proven to reduce the risk of HZ in patients receiving autologous hematopoietic-cell transplants for non-Hodgkin or Hodgkin lymphoma.57

In another trial, the 4-dose ZVHT was safe and elicited significant VZV-specific T-cell response through 28 days in immunosuppressed patients with solid tumor malignancy, hematologic malignancy, human immunodeficiency virus infection with CD4 counts of 200 cells/mm3 or less, and autologous hematopoietic-cell transplants. The T-cell response was poor in allogeneic hematopoietic-cell transplant recipients, however.58

Because the HZ/su vaccine does not contain live virus, it seems particularly promising for immunocompromised patients. In phase 1 and 2 studies, a 3-dose regimen has been shown to be safe and immunogenic in hematopoietic-cell transplant recipients and HIV-infected adults with CD4 count higher than 200 cells/mm3.59,60 A phase 3 trial assessing the efficacy of HZ/su vaccine in autologous hematopoietic-cell transplant recipients is under way (NCT01610414). Changes in recommendations for HZ vaccine in these most vulnerable populations await the results of these studies.

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