Newer Herpes Zoster Vaccine Effective Even in Older Adults

Laurie Barclay, MD

April 30, 2015

A recombinant subunit vaccine significantly lowered the risk for herpes zoster in adults aged 50 years or older without immunosuppressive conditions, according to a randomized, placebo-controlled, phase 3 trial. The study, published online April 28 in the New England Journal of Medicine, showed similar vaccine efficacy in adults who were 70 years of age or older as that seen in adults in their 50s and in their 60s.

In phase 1 and 2 trials, the experimental vaccine, which contains VZV glycoprotein E and the AS01B adjuvant system (called HZ/su, GlaxoSmithKline Biologicals), elicited a strong immune response that lasted for at least 3 years in adults and had an acceptable safety profile, even in adults with immunosuppression, note Himal Lal, MD, from GSK Vaccines, King of Prussia, Pennsylvania, and colleagues.

The current phase 3 trial, called the Zoster Efficacy Study in Adults 50 Years of Age or Older, aimed to determine whether two doses of HZ/su would safely lower the risk for herpes zoster among adults at least 50 years of age. Participants, who were stratified according to age group (50 - 59 years, 60 - 69 years, and ≥70 years), received two intramuscular doses of the vaccine or placebo 2 months apart.

Of 15,411 participants who could be evaluated, 7698 received HZ/su vaccine and 7713 received placebo. During a mean follow-up time of 3.2 years, six participants in the vaccine group developed herpes zoster, as did 210 participants in the placebo group (incidence rate, 0.3 vs 9.1 per 1000 person-years).

Vaccine Efficacy Did Not Decline With Age

Vaccine efficacy against herpes zoster was 97.2% overall (95% confidence interval [CI], 93.7% - 99.0%; P < .001). Moreover, the efficacy did not decline with age, at 96.6% (95 CI, 89.6% - 99.3%) among participants aged 50 to 59 years, 97.4% (95 CI, 90.1% - 99.7%) among those aged 60 to 69 years, and 97.9% (95 CI, 87.9% - 100.0%) among those aged 70 years or older.

Thus far, the vaccine has not given rise to any serious safety concerns.

Compared with the placebo group, the vaccine group had higher rates of solicited reports of injection-site and systemic reactions within 7 days after vaccination. Solicited or unsolicited reports of grade 3 symptoms preventing normal activities occurred in 17.0% (95 CI, 15.9% - 18.2%) of the vaccine group and in 3.2% (95 CI, 2.7% - 3.8%) of the placebo group. Both groups had similar mortality and proportions of participants who had serious adverse events or potential immune-mediated diseases.

"The age-independent efficacy of HZ/su is of clinical interest, since the incidence and severity of herpes zoster are higher among older adults," the study authors write. "HZ/su may thus provide a benefit to the population with the greatest medical need."

Limitations of this study include the need to maintain participant-level study blinding.

Need to Balance Efficacy With Risk

In an accompanying editorial, Jeffrey I. Cohen, MD, from the Laboratory of Infectious Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, notes that "results for this vaccine are promising and may provide an important addition to vaccinations for an aging population."

However, he discusses the need to balance immune response with risk for adverse effects. The rate of solicited systemic adverse reactions with HZ/su was 2.2 times as high in the vaccine group as in the placebo group (66% vs 30%). Grade 3 systemic reactions occurred in 11.4% of the vaccine group and in 2.4% of the placebo group and lasted a median of 1 day.

In contrast, a previous study of the currently used live attenuated vaccine showed rates of systemic adverse events similar to those seen with placebo (25% vs 24%, respectively).

"However, the rates of serious adverse reactions and potential immune-mediated diseases [with KZ/su] (a theoretical concern associated with the use of adjuvants) were similar in the two groups," Dr Cohen writes. "Since autoimmune diseases are more common among the elderly, it will be important to follow patients receiving this adjuvanted vaccine."

In addition to high efficacy even with increasing age, HZ/Su may have other advantages over live attenuated vaccine, and an ongoing trial is comparing the efficacy and safety of these two vaccines. For safety reasons, the current live attenuated vaccine is contraindicated in persons with impaired cellular immunity.

"Since the HZ/su vaccine contains only a single virus protein and therefore cannot replicate, it will probably be safer in such patients, although it is unclear whether the vaccine will elicit a sufficiently protective immune response," Dr Cohen writes. "A phase 1–2 trial of the HZ/su vaccine involving patients who had undergone autologous hematopoietic-cell transplantation showed that it induced VZV-specific CD4+ T cells that persisted for up to 1 year."

Recently completed research should help determine whether HZ/Su prevents postherpetic neuralgia and other complications of herpes zoster in the elderly, as well as the need for booster doses.

"The live attenuated vaccine significantly reduces the burden of illness caused by herpes zoster for 10 years after vaccination but significantly reduces the incidence of herpes zoster for only 8 years," Dr Cohen concludes. "Since the mean follow-up in the study of the HZ/su vaccine was 3.2 years, it will be important to determine the duration of its effect."

GlaxoSmithKline Biologicals funded this study and has financial relationships with some of its authors. Some of the other study authors reported various financial disclosures involving Pfizer, Merck, BioCSL Sanofi Pasteur MSD, Novartis, and Merck Sharp & Dohme.

N Engl J Med. Published online April 28, 2015. Full text


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