Annals of Long Term Care

Prevention of Herpes Zoster in Older Adults: Where Do We Stand with the Herpes Zoster Vaccine?
Michael N. Oxman, MD

Why do we need a herpes zoster (HZ) vaccine? First, there are more than 1 million new cases of HZ in the United States each year, and that number will increase as the population ages.^1,2 Second, once HZ develops, no treatment presently available, including early antiviral therapy (with or without corticosteroids) and pain medications, can prevent the most frequent debilitating complication of HZ, postherpetic neuralgia (PHN).^3,4

In 1965, based upon an analysis of all cases of HZ that occurred in his medical practice over a period of 16 years, Dr. R. Edgar Hope-Simpson5 published a series of important observations and a theory of the pathogenesis of HZ and PHN. He observed that the incidence and severity of HZ, as well as the incidence of PHN, increased with increasing age, and he hypothesized that this was because of an age-related decline in the immunity to varicella zoster virus (VZV) that originally developed in response to chickenpox. Hope-Simpson also observed that second episodes of HZ were relatively uncommon in healthy immunocompetent adults (in contrast to herpes simplex, which recurs repeatedly), and he hypothesized that this was because the large amount of viral antigen produced by VZV replicating in the skin and neuraxis during an episode of HZ boosts immunity to VZV, essentially “immunizing” the afflicted individual against another episode of the disease.⁵ During the past 40 years, evidence from many investigators has validated every aspect of Hope-Simpson’s prescient hypothesis, and has demonstrated that the component of the host immune response that determines susceptibility and resistance to HZ is cell-mediated immunity (CMI) rather than humoral immunity.^6,7

In the early 1970s, Dr. Michiaki Takahashi isolated VZV from a child in Japan with chickenpox and attenuated the virus by serial passage in cell culture. The resulting Oka strain of live attenuated VZV induced immune responses in susceptible children and adults that resembled those induced by natural varicella.⁸ Live attenuated Oka/Merck varicella vaccine was licensed in the United States in 1995 for the prevention of varicella in susceptible children and adults. Since then, widespread childhood immunization with varicella vaccine has nearly eliminated varicella and its complications in the United States.⁹

Based upon Hope-Simpson’s observations and hypothesis, my colleagues and I hypothesized that immunization of older adults with a VZV vaccine would boost their waning CMI to VZV and, thereby, provide protection against HZ and PHN.^1,7 However, since older adults already have significant immunity to VZV, as evidenced by their immunity to varicella, a much larger amount of VZV is required to induce a meaningful increase in VZV-specific CMI than is required for primary immunization of a child who has never been exposed to VZV. Consequently, the minimum potency of the investigational zoster vaccine used in the Shingles Prevention Study (see below) was at least 14 times greater than the minimum potency of live attenuated Oka/Merck varicella vaccine.¹

The Shingles Prevention Study
The Shingles Prevention Study (Department of Veterans Affairs [VA] Cooperative Study #403)1 was designed to test the hypothesis that imitating the immune response to VZV induced by an episode of HZ by administering a highpotency VZV vaccine would protect older adults from HZ and PHN. Several problems had to be addressed in order to carry out the study. Important among these is the assessment of outcomes.

Pain is the major cause of morbidity in HZ, especially among older adults, and thus pain should be a primary outcome measure. However, pain is subjective.