A new two-dose herpes zoster vaccine called HZ/su is safe and reduces the risk for shingles and postherpetic neuralgia by nearly 90% in people aged 70 years and older, according to a study published in the September 15 issue of the New England Journal of Medicine.
"The results of the current trial, which involved a population of adults 70 years of age or older, are consistent with those of a parallel study involving adults 50 years of age or older (ZOE-50), in which HZ/su was shown to have an efficacy of 97.9% for the prevention of herpes zoster in a smaller population of adults 70 years of age or older. Vaccine efficacy for the prevention of herpes zoster in adults 70 years or age or older did not differ significantly between these two studies." write first author Anthony Cunningham, MD, from the Westmead Institute for Medical Research and the University of Sydney, Australia, and members of the Zoster Efficacy Study in Adults 70 years of Age or Older (ZOE-70) study group.
Shingles, or herpes zoster, typically affects older people, and is painful rash caused by reactivation of latent varicella-zoster virus. Postherpetic neuralgia represents the most common complication, causing chronic pain that can negatively affect daily activities.
HZ/su is an investigational vaccine that contains recombinant varicella-zoster virus glycoprotein E. It also includes an adjuvant called AS01B designed to enhance CD4+ T-cell-mediated immune responses and improve vaccine efficacy.
As reported previously by Medscape Medical News, the Zoster Efficacy Study in Adults 50 Years of Age or Older (ZOE-50 trial), which included adults age 50 years and over, showed an overall vaccine efficacy of 97.2% across all age groups compared with placebo.
The ZOE-70 trial was designed to investigate the safety and efficacy of the HZ/su vaccine against shingles in adults aged 70 years and older.
The randomized placebo-controlled phase 3 trial took place at the same sites as ZOE-50 in 18 countries in Europe, North and South America, and Asia-Australia, and included 13,900 participants (mean age, 75.6 years; 54.0% from Europe; 76.9% white; 54.9% female). Researchers randomly assigned participants to two doses of the HZ/su vaccine injected intramuscularly 2 months apart (n=6950), or placebo (n=6950).
During a mean follow-up of 3.7 years, 23 participants in the HZ/su group developed laboratory-confirmed shingles compared with 223 in the placebo group.
The HZ/su vaccine had an efficacy against herpes zoster of 89.8% (95% confidence interval [CI], 84.2% - 93.7%; P < .001), with similar efficacy for participants aged 70 to 79 years (90.0%) and those aged 80 years and older (89.1%).
Pooled analyses of the ZOE-70 and participants aged 70 years and older in the ZOE-50 trial (16,596 participants) showed a vaccine efficacy against herpes zoster of 91.3% (95% CI, 86.8% - 94.5%; P < .001), with similar efficacy for ages 70 to 79 years (91.3%) and 80 years and older (91.4%).
In the pooled analysis, vaccine efficacy against postherpetic neuralgia was 88.8% (95% CI, 68.7%-97.1%; P < .001).
The HZ/su vaccine showed little decline in efficacy throughout the trial (year 1: 97.6%; year 2: 92.0%; year 3: 84.7%; year 4: 87.9%). Efficacy over even longer periods requires further study, the authors point out.
Compared with placebo, the HZ/su group reported more injection site reactions (9.9% vs 74.1%, respectively), and more systemic reactions (53.0% vs 25.1%, respectively) within 7 days of injection.
Both groups reported similar rates of serious adverse events (16.6% in the HZ/su group vs 17.5% in the placebo group), potential immune-related diseases (1.3% vs 1.4%), and deaths (6.1% and 6.6%). The rate of serious adverse events judged to be related to trial interventions by investigators were also similar between the two groups, at 0.2% in vaccine group and 0.1% in the placebo group.
Given the similar vaccine efficacy seen in ZOE-50 and ZOE-70, the authors suggest that efficacy does not decline with age of the patient. In contrast, studies have suggested that the efficacy of the currently approved live attenuated vaccine (Zostovax) declines with age
In a linked editorial, Kathleen Neuzil, MD, MPH, from the University of Maryland School of Medicine, Baltimore, and Marie Griffin, MD, MPH, from Vanderbilt University Medical Center, Nashville, Tennessee, highlight the lower efficacy of the Zostavax vaccine: 51.3% against shingles and 66.5% against postherpetic neuralgia, according to one large placebo controlled trial published in the New England Journal of Medicine. Studies have also suggested declining efficacy over time with the currently approved vaccine.
"Given the limited efficacy and duration of Zostavax, newer vaccine formulations with improved efficacy are welcome," they write.
HZ/su could be a "major advance" in preventing herpes zoster in immunocompromised individuals who cannot receive the live attenuated vaccine, they continue. Another "major benefit" of the HZ/su vaccine compared with the currently available vaccine may be improved efficacy in the oldest individuals. However, comparing efficacy across trials may be problematic because of differences in methodology and study populations, they caution.
While noting the "reassuring" safety profile of HZ/su, they say more safety data are needed, especially given the immune-enhancing properties of the new adjuvant.
Ultimately, the editorialists emphasize that the healthcare establishment will need to address barriers to delivery and uptake of the new vaccine.
"Although HZ/su may address some of these issues, such as easier storage requirements for a nonreplicating product, it will have its own challenges, including the two-dose schedule and the higher reactogenicity," they conclude.
On the basis of the newly reported data and the ZOE-50 data, GlaxoSmithKline said in a related news release that the company expects to submit regulatory applications for the candidate vaccine for the prevention of shingles in people aged 50 years and older later this year.
The study was funded by GlaxoSmithKline Biologicals. Several authors are employees or former employees of GlaxoSmithKline. Dr Heineman currently works for Genocea Biosciences. Dr Lal currently works for Pfizer. Dr Godeaux currently works for Crucell Holland. In addition, one or more authors reports receiving consulting fees, company stock, lecture fees, grant support, advisory board membership, patent royalties, honoraria, travel support, and/or personal fees from one or more of the following: Merck, BioCSL/Sequirus, GSK, Pfizer and Gilead Sciences, Sanofi Pasteur MSD, Novartis, Maruho and Japan Vaccines, Mochida, Astellas, Ferring, Forest, Novo Nordisk, Janssen-Ortho, Bayer, Wyeth, Combinator, Pharmanet, AstraZeneca, Lundbeck, Bristol-Myers Squibb, Romark, McNeil, Johnson & Johnson, Valneva, AbbVie, and/or Wyeth. One editorialist reports being an Investigator in Shingles the Prevention Study 2000-2011. Dr Neuzil reports being on the ACIP herpes zoster vaccine working group.
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Cite this: New Shingles Vaccine May Have Higher Efficacy in Older Adults - Medscape - Sep 15, 2016.