This article is adapted from Dr. John Russell’s Expert Presentation, "Guideline Update: Zoster Vaccination." To watch a streaming version of this presentation, click here .
- On October 20, 2017, a zoster vaccine recombinant adjuvant by GlaxoSmithKline plc. (GSK) known as Shingrix was approved by the FDA as a 2-dose vaccine.
- On January 26, 2018, the Advisory Committee on Immunization Practices (ACIP) recommended that this vaccine be administered to all immunocompetent adults older than 50 years.
What is varicella-zoster virus?
- Varicella-zoster is a very common, painful condition. "Zoster" was derived from a belt worn in ancient Greece, and it is thought that "shingles" is derived from "cingulum," which is also a girdle.
- Herpes zoster (shingles) is caused by a reactivation of a latent varicella-zoster virus infection. It can occur years or decades after our primary infection with chickenpox.
- It is generally associated with normal aging and with anything that causes reduced immunocompetence. Our lifetime risk in the United States is about 32%, and we have roughly 1 million cases of zoster diagnosed annually.
CDC. https://www.cdc.gov/shingles/about/overview.html. Updated January 2018. Accessed February 2018.
Previous vaccine: zoster vaccine live
- A previous single zoster vaccine that we had until recently, Zostavax (Merck & Co., Inc., Kenilworth, NJ, USA), contained live attenuated varicella virus in an amount that is approximately 14 times greater than that in regular varicella vaccine. It was recommended by the ACIP for patients 60 years of age and older. It was administered by a subcutaneous route.
- Per unpublished data by the CDC in 2016, about one-third of US adults older than 60 years had received this vaccine.
- What were the background studies for Zostavax, or zoster vaccine live (ZVL)? There was a trial, the Shingles Prevention Study, that looked at more than 38,000 adults older than 60 years and found the vaccine was about 51% effective in preventing shingles and about 67% effective in preventing postherpetic neuralgia. As they followed up this study in the Shingles Prevention Study, at 7-11 years they found the efficacy was only about 21%. The authors were not clear whether a "booster" dose would be effective at this point.
Oxman MN, et al. N Engl J Med. 2005;352:2271-2284.
Harpaz R. Update on Herpes Zoster. ACIP Meeting; June 24-25, 2015: Atlanta, Georgia.
2008 ACIP recommendations
- That led to the 2008 ACIP recommendations for zoster vaccine, which was a single dose of zoster vaccine for adults 60 years of age and older, whether or not they had reported a prior episode of shingles.
- Persons with a chronic medical disease may be vaccinated unless there was a contraindication or precaution for this condition.
CDC. Morb Mortal Wkly Rep. 2008;57(05):1-30.
New vaccine: recombinant zoster vaccine
- On October 20, 2017, a zoster vaccine recombinant adjuvant by GSK known as Shingrix was approved by the FDA as a 2-dose vaccine.
2017/2018 ACIP recommendations
- On October 25, 2017, the ACIP recommended this recombinant zoster vaccine (RZV) for use in immunocompetent adults.
- The recommendations of the RZV, or Shingrix, is recommended as a 2-dose vaccine given 2-6 months apart intramuscularly in immunocompetent adults older than 50 years.
- They did not study giving the second dose beyond 6 months, so although this may still work, there are no data to support it.
- We can give the vaccine irrespective of a prior recipient having the ZVL (Zostavax). We can give it with a previous history of zoster, and we do not need to screen our patients for varicella before giving this vaccine.
- Interestingly, it was given a preferential recommendation over the ZVL, which is a very unusual recommendation for the ACIP to give: to recommend 1 particular brand of vaccine over another.
Dooling KL, et al. Morb Mortal Wkly Rep. 2018;67(3):103-108.
Evidence for the new recommendations
- What are the background data? There was the ZOE-50 trial that looked at more than 15,000 participants who were randomly assigned to either a vaccine or placebo in a randomized, placebo-controlled, phase 3 trial. In these patients, who were placed in groups between 50 and 59, 60 and 69, and older than 70 years of age and who all received 2 doses of the vaccine 2 months apart, following them for 3.2 years they found an overall vaccine efficacy against zoster to be 97.2%. The vaccine efficacy was between 96.6 and 97.9 for all age groups, and the proportions of participants who had serious adverse events or potential immune-mediated diseases or who died were similar between the 2 groups.
Lai H, et al. N Engl J Med. 2015;372:2087.
- Another study that looked at an older population, published in the New England Journal of Medicine, was a randomized, placebo-controlled trial of more than 13,000 adults older than 70 years, with a mean age of 75 years; 22% of the patients were older than 80 years. They were given the RZV, the adjuvant vaccine, or placebo 2 months apart and were followed-up for 3.7 years. The vaccine was found to be 89.8% effective. In a pooled evaluation of patients older than 70 years in this study, it was 91.3% effective against zoster and 88.8% effective against postherpetic neuralgia, and that was combining some of the data from the previous trial. It did have a local reaction rate of 79% vs 25%.
Cunningham AL, et al. N Engl J Med. 2016;1019-1032.
A closer look at the new recommendations
- Let us look at these recommendations from the ACIP that were published in the Morbidity and Mortality Weekly Report on January 26, 2018: We would recommend this vaccine to all immunocompetent adults older than 50 years, we should give the vaccine 2-6 months apart, and it should be a 0.5-mL intramuscular shot. Timing: We should not give our vaccine with an active zoster infection, and based on expert opinion, if someone had received the other vaccine, the ZVL, we should wait more than 2 months to give this vaccine. It can be given at other sites with other adult vaccines. Patients with chronic medical diseases may receive the RZV. It is recommended for those receiving low-dose immunosuppression; for example, a prednisone equivalent of less than 20 mg a day.
- It has not been studied with moderate- to high-dose immunosuppressive therapy, and that issue should be discussed at further ACIP meetings. It also has not been studied in varicella-negative patients, but we should not be screening our patients to determine whether they have had varicella before.
- Contraindication is severe allergy or anaphylaxis to any component of the vaccine.
- We should not give it to our patients who are pregnant or lactating; it has not been studied in those situations.
John Russell, MD, is clinical professor of family and community medicine at Thomas Jefferson University, Sydney Kimmel School of Medicine, Philadelphia, Pennsylvania, and family medicine residency program director at Abington Hospital-Jefferson Health, Abington, Pennsylvania. Disclosure: Dr. Russell is on the speakers’ bureau for Sanofi Pasteur.