Phase 3 Trial of Recombinant Shingles Vaccine Shows Promise in Older Adults

Phase 3 Trial of Recombinant Shingles Vaccine Shows Promise in Older Adults

July 15, 2015 Karie Youngdahl

Shingles on face and in mouth, 1835The herpes zoster vaccine commercially available in the United States (Zostavax, Merck, generic zoster vaccine live) is 51% effective at preventing shingles in adults ages 60 and older, but it is less effective for older adults. For those over age 70, it is only 38% effective at preventing disease. Vaccine maker GSK hoped to produce a vaccine that worked better for older adults and that could be used by people with immunosuppressive conditions. (The licensed zoster vaccine is a live, attenuated virus vaccine and so is contraindicated in people with suppressed immune systems.)

The antigenic material in the GSK vaccine is a recombinant varicella zoster glycoprotein that elicits an immune response. Because it is only a subunit of the whole virus, the glycoprotein does not reproduce in the vaccinee, and so theoretically it is safe for people with suppressed immune systems. The vaccine uses a two-component adjuvant to boost immune response. One component is a molecule called monophosphoryl lipid A; it is found on the surface of certain bacteria and evokes an immune response in humans. The other adjuvant component comes from the soapbark tree, an evergreen plant native to South America. 

In late April the New England Journal of Medicine published the results of a Phase 3 study of the GSK vaccine HZ/su. This randomized control trial took place on on five continents. The study analysis included 15,422 participants, 7,361 of whom received two doses of the vaccine (337 received only one dose of vaccine). The 7,713 participants in the control arm of the trial received saline placebo injections. 

All participants were age 50 and older, and none had a history of shingles disease or had been vaccinated with chickenpox or shingles vaccine, and none were immunosuppressed.

Vaccine efficacy across the entire group that received two doses of vaccine was 97.2% (95% confidence interval [CI], 93.7 to 99.0; P<0.001). Importantly for this vaccine, efficacy did not change with increasing age (for ages 70+, vaccine efficacy was 97.9% [95% CI 87.9-100.0]. Side effects were mainly pain at the injection site and myalgia. Serious AEs, such as heart attack, were similar in vaccine and placebo groups.

GSK will likely request approval from the US FDA based on the Phase 3 trial results.

I asked one of my advisors, Thomas Fekete, MD, chief of the infectious diseases section at Temple University Hospital, to comment on the new vaccine and what people might do as it makes its way through the approval process. He said, “What’s better than having a good vaccine that can prevent over half the cases of a highly annoying disease? Having an even better vaccine that is more effective in prevention and whose effect lasts longer. We will soon see if the successor to the current vaccine to prevent shingles (also called zoster) lives up to the early hype. If so, we might further reduce the number of people suffering from shingles and its dreaded sequela, post-herpetic neuralgia. The latter is a persistent and painful condition that lingers after the healing of shingles. Pain management for this condition is challenging and it tends to affect elderly and vulnerable folks. It may be a few years before this new vaccine is available, so for now it's prudent to get the current vaccine if you are over the age of 60 and have no serious immune disease.”

Image from Rayer, Pierre François Olive, 1793-1867. Traité théorique et pratique des maladies de la peau (Paris : Chez J. B. Bailliere, 1835), plate 1. ZJa 8a (Historical Medical Library of the College of Physicians of Philadelphia)

Reference

Himal L, Cunningham Al, Godeaux O, Chlibek R, Diez-Domingo J, Shann-Jan H, … Heineman TC. Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults. New England Journal of Medicine. 2015;373(22):2087-2096. Retrieved from http://www.nejm.org/doi/full/10.1056/NEJMoa1501184&nbsp;

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