A Shingles Vaccine

Abstract & Commentary

By Stan Deresinski, MD, FACP, Clinical Professor of Medicine, Stanford; Associate Chief of Infectious Diseases, Santa Clara Valley Medical Center is Editor for Infectious Disease Alert

Synopsis: The use of an attenuated varicella zoster virus vaccine, many times more potent than that used in children for the prevention of chickenpox, was effective in the prevention of both herpes zoster and postherpetic neuralgia in individuals 60 years of age and older.

Source: Oxman MN, et al. A Vaccine to Prevent Herpes Zoster and Postherpetic Neuralgia in Older Adults. N Engl J Med. 2005;352:2271-2284.

Oxman and colleagues randomized 38,546 subjects greater than 60 years of age (median age, 69 years) to receive either 0.5 mL of attenuated Oka/Merck VZV vaccine or placebo, after which they were followed for a mean duration of 3.13 years, during which they were contacted monthly. The vaccine was well tolerated, although approximately one-third to one-half of recipients developed erythema, pain, and/or tenderness at the injection site.

Herpes zoster was confirmed in 315 vaccine recipients and 642 of those assigned placebo, a 61% vaccine-associated reduction. The incidences per 1000 person-years were 5.42 and 11.12, respectively. The efficacy of the vaccine in preventing zoster was lower in those 70 years of age or greater for whom it was 37.6% vs 63.9% in those 60 to 69 years (< 0.0010). VZV DNA was detected by PCR in more than 93% of cases—none had vaccine-type DNA.

Antiviral treatment was administered to 87.3% of those in the vaccine group who developed zoster and to 85.7% in the placebo group, and was initiated within 72 hours in 64.1% and 65.9%, respectively. In addition, similar analgesic usage occurred in the 2 groups. Despite this similar management, the burden-of-illness score, representing the average severity of illness during the 182 days after the onset of rash in the population as a whole, was reduced 61.1% (P < 0.001) in vaccine recipients, when compared to the placebo group. Twenty-seven vaccine recipients and 80 in the placebo group developed postherpetic neuralgia, representing 0.46 and 1.38 cases per 1000 person-years, respectively (P .0.001), for an efficacy of 66.5%.

Commentary

It is estimated that at least 1 million cases of herpes zoster occur yearly in the United States, with most occurring in those 50 years of age and older. The acute infection is debilitating, and the development of postherpetic neuralgia even more so. Antiviral therapy shortens the duration of clinical zoster, but has no effect on prevention of postherpetic neuralgia, which may persist for a year or more in as significant proportion of those affected. The aging of the population is providing an increasing number of individuals at risk of developing zoster. Furthermore, the successful use of the pediatric varicella vaccine, Varivax®, means that adults will encounter VZV less frequently, thus missing the opportunity to boost cell mediated immunity to the virus, a phenomenon that continues as we age. Thus, the results reported by the Shingles Prevention Study Group reviewed above are most welcome.

The vaccine used in the Shingles Prevention Study is not the same as that in use in pediatrics. The experimental attenuated zoster vaccine used here had a potency at least 14 times greater than that of Varivax®, as measured by the number of plaque-forming units administered. The higher dose was chosen because of evidence that lower doses were unable to reliably boost cell mediated immunity against VZV in the elderly.

It can be hoped that this vaccine will be available for use in the near future. One wonders, however, if it will prove possible to identify a subset of the population, in addition to those with known significant immune compromise, who are at increased risk of developing zoster and who might be more specifically targeted for vaccination.