Shingles (Herpes Zoster): a more Effective Vaccine (also in Older People)

Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults.
Lal H, Cunningham AL, Godeaux O, Chlibek R, Diez-Domingo J, Hwang SJ, Levin MJ, McElhaney JE, Poder A, Puig-Barberà J, Vesikari T, Watanabe D, Weckx L, Zahaf T, Heineman TC; ZOE-50 Study Group.
N Engl J Med. 2015 May 28;372(22):2087-96. doi: 10.1056/NEJMoa1501184. Epub 2015 Apr 28.

Shingles (Herpes Zoster) is a common disorder caused by the reactivation of the Varicella Zoster Virus (VZV) in individuals who had chicken pox (90% of individuals were infected, usually in childhood)

The disorder presents as vesicules clustered in crops (Herpetiform) which are usually limited to a dermatome. Involvement of multiple dermatomes should raise the suspicion of immunodeficience (such as in HIV infection)
Lesions are usually preceded by a tingling/burning sensation.

Shingles usually self-limiting and recovery can be speed up by the use of antivirals (such as acyclovir)

In individuals over 55-60, pain can remain after the ocurence of the active episode and this justifies the use of a vaccine in this population group. Indeed post-herpetic neuralgia is an often difficult to manage condition in hospital outpatient pain-units.

A vaccine is already present but it is not universally efficient:
-Indeed, the Zostavax vaccine (Merck) showed an around 50% efficacy against herpes zoster and a 66.5% efficacy against postherpetic neuralgia in individuals over 60
-Also the vaccine becomes less effective after 70 (=37.6%)
-Also this is a live attenuated vaccine and is contraindicated in individuals with immunosuppression

In this US study, published in the New England Journal of Medicine authors demonstrate the safety and efficacy of a subunit of VZV consiting of glycoprotein E and the AD01 adjuvant system (HZ/su, Glaxo Smith Kline (GSK)). It is a recombinant (non-living) subunit vaccine.

Methods
-phase 3 study (safety and efficacy already suggested in Phase 1 and 2 studies)
-15411 individuals over 50 (divided into 3 groups* 50-59, 60-69, over 70)
–2 intramuscular doses of vaccine* compared with placebo

Results
–6 individuals vaccinated developed Shingles (7698 received the vaccine) in in 3.2 mean follow up period (210 individuals developed shingles in the placebo group (n=7713)
-This amounts to an overall efficacy of 97.2% efficacy of the vaccine. The efficacy of the vaccine in individuals over 70 remained similar to the 2 other age groups.
–Mild self-limiting local reactions were present in 17% of cases (vs 3% placebo): injection site reaction (in around 80% of cases, systemic reaction (66%, myalgia, fatigue, headache, shivering, fever, gastrointestinal symptoms)
-Severe reactions and the death rate was similar in treated and untreated groups

Conclusion
This non-live vaccine appears to offer (at the time of publication) the best preventive options against Herpes Zoster (Shingles) and its accompanying persisting pain.

Comment
-Phase 2 (Phase 1 studies need mainly to show safety, Phase 3 studies concern larger groups). Phase 3 studies are needed before the drug is approved, marketable, and eventually reimbursed (country-to-country basis)
-Phase 3 studies needs to demonstrate superior efficacy when compared to the cost to be remibursed US vc UK (Nice National Institute for Clinical Excellence)
-It is not surprising therefore that this study is performed by GSK Pharmaceuticals, the company who develops the vaccine.

*[The HZ/su vaccine contains 50 μg of recombinant VZV glycoprotein E and the liposome-based AS01B adjuvant system containing 50 μg of 3-O-desacyl-4′-monophosphoryl lipid A (MPL) and 50 μg of Quillaja saponaria Molina, fraction 21 (QS21)]

Article selection: Prof Dr Jean-Hilaire Saurat – dermatologist. Geneva, Switzerland