A Review of the Shingles Vaccine SHINGRIX

The recombinant zoster vaccine SHINGRIX is highly effective for prevention of the viral infection herpes zoster — commonly known as shingles — as well as serious long-term complications of the infection. The vaccine also carries a very low risk of serious adverse effects. Public Citizen’s Health Research Group therefore has concluded that the benefits of vaccination with Shingrix outweigh the risks.

The Food and Drug Administration (FDA) initially approved Shingrix in 2017 for prevention of shingles in adults aged 50 and older.[1] In July 2021, the FDA approved the vaccine for use in adults aged 18 and older who are or will be at increased risk of herpes zoster due to immunodeficiency or immunosuppression caused by known existing disease or therapy (immunocompromised individuals).[2]

Shingrix, which contains a purified synthetic version of a protein found on the outer surface of the varicella-zoster virus that causes herpes zoster,[3] supplanted the older shingles vaccine, ZOSTAVAX, which contained a weakened form of the virus and was withdrawn from the U.S. market in 2020 because it was much less effective than Shingrix, especially in older adults.[4]

Shingrix is administered by injection in the upper arm in two doses separated by two to six months for adults who are not immunocompromised and by one to two months for immunocompromised individuals.[5]
 

Important Facts About Shingles

Shingles is an infection caused by a herpes virus called varicella-zoster, the same virus that causes chickenpox. After chickenpox resolves, the virus remains dormant in the body’s nerves for years or even decades without causing symptoms.[6] The virus commonly reactivates in adults, causing the painful condition known as herpes zoster or shingles. The Centers for Disease Control and Prevention estimates that about one-third of people in the U.S. will develop shingles during their lifetime.[7]

Shingles typically develops in a single stripe around one side of the body or on one side of the face, often beginning as pain, itching or tingling, before manifesting as a rash over the same area within several days.[8] The rash consists of blisters that usually scab over in seven to 10 days, and it typically clears up completely, even without treatment, within two to four weeks.[9] Other symptoms can include fever, headache, chills and upset stomach.

The most common complication of shingles is long-term nerve pain, a condition known as postherpetic neuralgia.[10] This complication occurs in approximately 10–18% of people who have shingles.[11] The pain of postherpetic neuralgia can persist for months to years after the rash has resolved and can be severe and debilitating, interfering with daily life. The risk of postherpetic neuralgia increases with age, as does the severity and duration of this complication. Shingles on the face can affect the eye and cause vision loss. Shingles very rarely can lead to pneumonia, hearing loss, brain inflammation and death.[12]

Several antiviral medications — including acyclovir (ZOVIRAX), valacyclovir (VALTREX) and famciclovir (available in generic only) — can be used to treat shingles and shorten the length and severity of the infection,[13] but prevention with the shingles vaccine is more effective.

Significant clinical benefit

The effectiveness of Shingrix given in two doses separated by two months in adults aged 50 and older who are not immunocompromised was assessed in two randomized clinical trials. The first enrolled approximately 14,800 subjects aged 50 or older, and the second enrolled nearly 13,200 subjects aged 70 or older.[14] In each trial, half of the subjects received two doses of Shingrix, and the other half received two placebo injections. Subjects were followed for an average of three years in the first trial and about four years in the second.[15]

Results from these two trials revealed that Shingrix was 97% effective in preventing shingles in subjects aged 50 to 69 and 90% effective in subjects aged 70 or older.[16] The vaccine also was 100% effective in preventing postherpetic neuralgia in subjects aged 50-69 and 89% effective in subjects aged 70 or older.[17]

The effectiveness of Shingrix given in two doses separated by one month was assessed in immunocompromised adults aged 18 or older in two other randomized, placebo-controlled clinical trials. The first, which enrolled approximately 1,720 subjects who were immunocompromised because of a recent blood stem cell transplant, found that Shingrix was 68% effective in preventing shingles and 89% effective in preventing postherpetic neuralgia.[18] The second trial involved 515 subjects who were immunocompromised because of treatment for blood-cell cancer (for example, leukemia or lymphoma) and found that Shingrix was 87% effective in preventing shingles.[19]

Safety profile

Like many vaccines, Shingrix commonly causes multiple short-term adverse effects including the following:

• pain, redness and swelling at the injection site
• generalized muscle aches
• fatigue
• headache
• fever
• shivering
• gastrointestinal symptoms including nausea, vomiting, diarrhea and abdominal pain[20]

In most patients, these adverse effects were mild to moderate in severity.

In the large clinical trials of Shingrix that enrolled subjects aged 50 and older who were not immunocompromised, there were more than 14,000 subjects combined in the vaccine groups and 14,000 subjects in the placebo groups.[21] Of note, adverse events involving gout or gouty arthritis within 30 days following Shingrix or placebo injection occurred in 27 vaccine-group subjects and only eight placebo-group subjects.[22] Also, ischemic optic neuropathy (damage to the optic nerve due to decreased blood flow, which can result in impaired vision) was reported within 50 days following injection in three vaccine-group subjects and no placebo-group subjects. Overall, within 365 days following the last vaccine or placebo dose, there were no differences in the rates of death or overall serious adverse events between the vaccine-group subjects and the placebo-group subjects.[23]

In the smaller clinical trials of Shingrix in immunocompromised adults, similar short-term adverse effects were seen with the vaccine.[24] The only notable safety finding was a slightly higher frequency of pneumonia within 30 days after vaccination in vaccine-group subjects compared with placebo-group subjects.

Guillain-Barré syndrome

Importantly, data from a postapproval study that examined medical-claims data for Medicare beneficiaries who had been vaccinated with Shingrix from October 2017 to February 2020 found a very small increase in the risk of developing Guillain-Barré syndrome within 42 days following vaccination.[25] Specifically, the study researchers estimated that there were three additional cases of Guillain-Barré syndrome per million Shingrix doses in adults aged 65 or older beyond what would normally be expected in this population.

Guillain-Barré syndrome is a rare disorder in which the body’s immune system attacks the nerves. It has been linked to a variety of viral infections, including influenza and COVID-19, and occurs rarely following other vaccinations, including influenza vaccination.[26] Symptoms include weakness and tingling in the arms and legs, which can progress to complete paralysis.[27] The majority of people recover with treatment, but the syndrome is fatal in up to 7% of cases.[28]

What You Can Do[29]

You should get vaccinated with two doses of Shingrix if you are aged 50 or older and not immunocompromised, even if you had a prior episode of herpes zoster, a prior dose of the older shingles vaccine Zostavax, or are unsure if you had chickenpox.

You should not receive Shingrix if you are currently experiencing an episode of shingles; instead, talk to your doctor about whether you should be prescribed one of the antiviral drugs approved for treating shingles. Shingrix can be given after you have recovered from shingles.

You also should not receive Shingrix if you had a severe allergic reaction to a previous dose of Shingrix or if you are known to not have any antibodies in your blood against the varicella-zoster virus (you instead should receive the varicella virus vaccine [VARIVAX] for preventing chickenpox).

If you are aged 18 or older and may be immunocompromised, ask your doctor whether you should be vaccinated with Shingrix.
 

References

[1] Food and Drug Administration. Approval letter for the biologics license application for Zoster Vaccine Recombinant, Adjuvanted. October 20, 2017. https://www.fda.gov/media/108274/download. Accessed December 7, 2021.

[2] Food and Drug Administration. Approval letter for supplement for the biologics license application for Zoster Vaccine Recombinant, Adjuvanted. July 23, 2021. https://www.fda.gov/media/151063/download. Accessed December 7, 2021.

[3] Food and Drug Administration. Summary basis for regulatory action for Shingrix, BLA 125614/0. October 20, 2017. https://www.fda.gov/media/108954/download. Accessed December 7, 2021.

[4] Centers for Disease Control and Prevention. Vaccine and preventable disease. What everyone should know about Zostavax. October 5, 2020. https://www.cdc.gov/vaccines/vpd/shingles/public/zostavax/index.html. Accessed December 7, 2021.

[5] GlaxoSmithKline. Label: Zoster Vaccine Recombinant, Adjuvanted (SHINGRIX). July 2021. https://www.fda.gov/media/108597/download. Accessed December 7, 2021.

[6] Centers for Disease Control and Prevention. Shingles (herpes zoster). Transmission. July 1, 2019. https://www.cdc.gov/shingles/about/transmission.html. Accessed December 7, 2021.

[7] Centers for Disease Control and Prevention. Shingles (herpes zoster). About shingles (herpes zoster). June 26, 2019. https://www.cdc.gov/shingles/about/index.html. Accessed December 7, 2019.

[8] Centers for Disease Control and Prevention. Shingles (herpes zoster). Signs & symptoms. July 1, 2019. http://www.cdc.gov/shingles/about/symptoms.html. Accessed December 7, 2021.

[9] Ibid.

[10] Centers for Disease Control and Prevention. Shingles (herpes zoster). Complications of shingles. July 1, 2019. https://www.cdc.gov/shingles/about/complications.html. Accessed December 7, 2021.

[11] Ibid.

[12] Ibid.

[13] Centers for Disease Control and Prevention. Shingles (herpes zoster). Treating shingles. July 1, 2019. https://www.cdc.gov/shingles/about/treatment.html. Accessed December 7, 2021.

[14] Food and Drug Administration. Summary basis for regulatory action for Shingrix, BLA 125614/0. October 20, 2017. https://www.fda.gov/media/108954/download. Accessed December 7, 2021.

[15] Food and Drug Administration. BLA clinical review memorandum for Shingrix, BLA 125614. October 20, 2017. https://www.fda.gov/media/108786/download. Accessed December 7, 2021.

[16] Food and Drug Administration. Summary basis for regulatory action for Shingrix, BLA 125614/0. October 20, 2017. https://www.fda.gov/media/108954/download. Accessed December 7, 2021.

[17] Ibid.

[18] Food and Drug Administration. BLA clinical review memorandum for supplemental BLA 125614/398. July 23, 2021. https://www.fda.gov/media/151234/download. Accessed December 7, 2021.

[19] Ibid.

[20] Food and Drug Administration. Summary basis for regulatory action for Shingrix, BLA 125614/0. October 20, 2017. https://www.fda.gov/media/108954/download. Accessed December 7, 2021.

[21] Ibid.

[22] Ibid.

[23] Ibid.

[24] Food and Drug Administration. BLA clinical review memorandum for supplemental BLA 125614/398. July 23, 2021. https://www.fda.gov/media/151234/download. Accessed December 7, 2021.

[25] Goud R, Lufkin B, Duffy J, et al. Risk of Guillain-Barré syndrome following recombinant zoster vaccine in Medicare beneficiaries. JAMA Intern Med. November 1, 2021. doi:10.1001/jamainternmed.2021.6227. Published online ahead of print.

[26] Mayo Clinic. Guillian-Barré syndrome. July 23, 2021. https://www.mayoclinic.org/diseases-conditions/guillain-barre-syndrome/symptoms-causes/syc-20362793. Accessed December 7, 2021.

[27] Ibid.

[28] Ibid.

[29] Centers for Disease Control and Prevention. Vaccines and preventable diseases. Shingrix recommendations. October 5, 2020. https://www.cdc.gov/vaccines/vpd/shingles/hcp/shingrix/recommendations.html. Accessed December 7, 2021.