A Closer Look at the Herpes Zoster Subunit Vaccine

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The high efficacy of the herpes zoster subunit vaccine that was found in this trial has many important implications.
The high efficacy of the herpes zoster subunit vaccine that was found in this trial has many important implications.

Herpes zoster may occur in persons of any age previously infected with the varicella zoster virus (chickenpox), but it is most common in adults > 60 years old experiencing an age-related decline in immunity. 

Zostavax (Merck), a live zoster vaccine, is recommended for adults ≥ 60 years old. Zostavax has a reported three-year efficacy of 51.3% against herpes zoster (absolute risk reduction of 1.7%), but this efficacy decreases with increasing patient age.


The first report of an ongoing phase 3 trial was recently published comparing a herpes zoster subunit vaccine vs. placebo in 15,411 immunocompetent adults ≥ 50 years old without history of herpes zoster, herpes zoster vaccination, or varicella vaccination. 

The subunit vaccine contained 50 mcg recombinant varicella-zoster virus glycoprotein E and a liposome-based AS01B adjuvant system. Two vaccination or placebo doses were administered to adults by intramuscular injection at baseline and two months (N Engl J Med. 2015;372[22]:2087)


All adults received at least one study drug dose and were included in the overall analysis. At randomization, 8,926 adults (58%) were assigned to a reactogenicity subgroup and asked to record solicited injection site and systemic reactions for 7 days on a diary card. During the mean 3.2 year follow up, there were 244 confirmed cases of herpes zoster (0.1% with vaccination vs. 3.1% with placebo, absolute risk reduction of 3%). 

The rate of herpes zoster per 1,000 person-years was 0.4 with the subunit vaccine and 9.3 with placebo in the overall cohort, giving a vaccine efficacy of 96.2%. These results were consistent across all age groups. Overall, serious adverse events were reported in 9% receiving the subunit vaccine and 8.9% receiving placebo. 

The reactogenicity subgroup reported a greater percentage of adverse events in the vaccination group within 7 days of administration (84.4% vs. 37.8%), but most were mild to moderate injection site or systemic reactions with grade 3 adverse events reported in 17% with vaccination and 3.2% with placebo. 


The high efficacy of the herpes zoster subunit vaccine found in this trial has many important implications. First, there appears to be greater overall efficacy compared to Zostavax. This subunit vaccine also shows no evidence of decreased immunogenicity with age. Finally, unlike the live zoster vaccine, it may also be safe for use in immunocompromised populations because the subunit vaccine does not contain a replicating virus with the potential to cause disease. 

Immunocompromised patients were excluded from this phase 3 trial, however, so further studies will be required to determine if this vaccine is safe for all older adults. Overall, the results of this trial suggest that this recombinant varicella-zoster virus glycoprotein E subunit vaccine is highly effective for preventing herpes zoster in older immunocompetent adults

The ongoing trial will continue to monitor patients for approximately 60 months to determine the vaccine efficacy over five years. 



Alan Ehrlich, MD, is a deputy editor for DynaMed, Ipswich, Mass., and assistant clinical professor in Family Medicine, University of Massachusetts Medical School in Worcester. 

DynaMed is a database that provides evidence-based information on more than 3,000 clinical topics and is updated daily through systematic surveillance covering more than 500 journals. 

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