Herpes Zoster Subunit Vaccine Has 96% 3-year Efficacy Against Herpes Zoster in Immunocompetent Adults ≥ 50 years old

EBM Focus - Volume 10, Issue 23

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Reference - N Engl J Med 2015 May 28;372(22):2087 (level 1 [likely reliable] evidence)

Herpes zoster (shingles) 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 (Ann Intern Med 2011 Mar 1;154(5):ITC31). Zostavax, a live zoster vaccine, is recommended for adults ≥ 60 years old, but it is not appropriate for adults with immunodeficiencies (MMWR Morb Mortal Wkly Rep 2015 Feb 6;64(4):91). Zostavax has a reported 3-year efficacy of 51.3% against herpes zoster (absolute risk reduction of 1.7%), but this efficacy decreases with increasing patient age (N Engl J Med 2005 Jun 2;352(22):2271). 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 2 months.

All adults received at least 1 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% (p < 0.001). 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 (no p value reported).

While the zoster subunit vaccine showed increased reactogenicity compared to placebo, most reactions were mild to moderate with a similar rate of serious adverse events reported in the overall cohort. 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 5 years.

For more information, see the Herpes zoster topic in DynaMed.


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