COMMENTARY

Shingrix: Is the Hype Justified?

Paul A. Offit, MD

Disclosures

February 13, 2018

Editorial Collaboration

Medscape &

Hi. My name is Paul Offit. I'm talking to you from the Vaccine Education Center at Children's Hospital of Philadelphia. I want to talk about a newly licensed and recommended shingles vaccine.

Shingles, as you know, is a reactivation of an original chickenpox infection that travels down a dermatome and causes rash and pain. It's a common infection—roughly 1 in every 1000 people every year in the United States will suffer shingles, and about 1 in 3 people in the United States will suffer shingles in their lifetime. Usually, shingles occurs in those > 65 years of age.

The pain of shingles is one of the worst pains in medicine. It's right up there with corneal abrasions, labor and delivery, and kidney stones (which is like labor and delivery for men)—an incredibly painful experience.

The first shingles vaccine was licensed and recommended in 2006. It's called Zostavax® and is a live, weakened form of the chickenpox (varicella) virus. In fact, Zostavax is the varicella vaccine; it's just 14 times the dose. The efficacy of Zostavax against rash was about 51%; the efficacy against postherpetic neuralgia (the pain associated with shingles) was about 67%, and the duration wasn't great. After about 4 years, the protective effect for postherpetic neuralgia went from about 67% down to about 30%.

Recently, in October 2017, another shingles vaccine was licensed and recommended. It's called Shingrix, and it's made in quite a biologically different manner. Instead of being a whole weakened form of the virus, it's just one protein that sits on the surface of the virus—the so-called glycoprotein E—and then two adjuvants are used. One adjuvant is called monophosphoryl lipid A (which is just a detoxified lipid A), the same adjuvant that was used in Cervarix®. The other is a novel adjuvant, one that we haven't used in this country before. It's called QS-21. It's a glycoside (specifically, saponin). The "QS" stands for the name of the tree (Quillaja saponaria) from which this product was purified. It's a soap tree indigenous to Chile. The "21" stands for the 21st chromatographic peak from which this saponin was isolated.

If you look at the efficacy of Shingrix against rash, it's not 51% (as was the case with Zostavax); it's in the mid- to high 90% range, for all age groups—even for those over 70 years of age.[1,2] Similarly, if you look at the protective efficacy against postherpetic neuralgia, it's in the high 80% to low-mid 90% range, and the duration is much greater—4 years later, the protective efficacy is still about 85%.[1,2]

How should this vaccine be used? This was the question faced by the Advisory Committee on Immunization Practices (ACIP) in October. They made the following recommendations[3]:

  • This vaccine can be given starting at 50 years of age;

  • It's a two-dose vaccine, with the second dose being given 2-6 months after the first;

  • It is the preferred vaccine—those who have not yet received a shingles vaccine should receive Shingrix rather than Zostavax; and

  • Even if you've already had Zostavax, it is still recommended that you receive two doses of the Shingrix vaccine.

It's pretty remarkable. Typically, the gold standard for inducing long-lived, highly effective protective immune responses is much better defined for live attenuated viruses than for purified protein (so-called "subunit vaccines"), but this is one of those rare examples—in fact, the only example I can think of—where the purified protein (the glycoprotein A) vaccine induces a better and longer lasting response than the live attenuated viral vaccine.

The side effect profile for systemic side effects (fever, myalgia, chills) is somewhat worse for Shingrix than for Zostavax, but that said, fewer than 5% of people who received Shingrix said that it interfered in any sense with their daily lives. So, it certainly looks like the better vaccine.

Thank you very much for your attention.

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