Herpes Zoster Vaccine: A Breakthrough in Preventing Shingles

Anna K. Morin, PharmD

Herpes zoster, also known as hz or shingles, is caused by the varicella zoster virus, or VZV, the same virus that causes chickenpox (1). VZV remains dormant in the body within the dorsal root ganglia and can reactivate years later, spreading along a sensory nerve to cause HZ. Not everyone who had chickenpox will develop shingles, but immunity to VZV declines with advancing age and the risk for developing shingles rises sharply after the age of 50. An estimated 1 million people get shingles annually in the United States with approximately one out of every three people developing shingles during their lifetime. The annual incidence for HZ in the U.S. is approximately five cases per 1,000 in adults aged 50-59 years. However, the estimated annual incidence among individuals 80 years and older more than doubles to 11 cases per 1,000 (1,2). Immunocompromised individuals are at greater risk of developing shingles (2). Because the risk of reactivation of vaccine-strain VZV is lower compared with reactivation of wild-type, non-vaccine strain, VZV, children who have been vaccinated against chickenpox have a lower risk of developing HZ (3). There is limited information on the impact of the chickenpox vaccine on the rate of HZ in those who received the vaccine as an adult. The economic and public health impact associated with HZ in the U.S. is significant. Estimated annual direct and indirect costs related to not being vaccinated for HZ in the U.S. are nearly $800 million and the costs associated with HZ in those over the age of 65 is projected to be $4.74 billion by 2030, if the incidence of HZ is not decreased (4).

Shingles presents as a painful maculopapular rash that commonly develops in one or two adjacent dermatomes and presents as a single strip on one side of the body, this is localized HZ (1,3). The rash most often appears on the trunk along a thoracic dermatome as blisters or vesicle clusters that typically scab over in seven to 10 days and fully clear within two to four weeks. Less commonly, the rash can be more widespread and affect three or more dermatomes, this is disseminated HZ (1,3). Disseminated zoster generally occurs in those with compromised or suppressed immune systems and can be difficult to distinguish from chickenpox. Symptoms of pain, itching or tingling may precede the onset of an HZ rash by several days. Most individuals experience a single episode of shingles during their lifetime. However, multiple episodes of shingles are possible.

Additional symptoms of shingles can include fever, headache, chills, fatigue and gastrointestinal upset. Shingles is not contagious, however, direct contact with the fluid in the HZ vesicles can lead to infection of VZV in those who are not immune — i.e., those who have never had chickenpox nor received the chickenpox vaccine (3). These individuals will develop chickenpox and be at risk for shingles later in life. Infection with VZV is not a concern before the shingles rash blisters appear or after the rash crusts. To prevent spreading VZV to others, patients with shingles should cover the rash, avoid touching or scratching the rash, wash their hands often and avoid contact with the following high-risk individuals during the blister stage: pregnant women, infants and immunocompromised individuals (1,3).

The most common complication of shingles is postherpetic neuralgia, or PHN, which is long-term nerve pain persisting for at least 90 days following the resolution of the HZ rash. It can be so severe and debilitating that it interferes with daily life (1,3). PHN can last for weeks, months and, rarely, for years after the rash clears. Overall, approximately 10 to 13% of persons 50 years or older who get shingles will experience PHN. Risk of developing PHN after HZ increases with age and older adults with shingles are more likely to experience longer lasting and more severe pain (2,3). Other predictors of PHN include the level of pain and the size of rash. Additional complications of HZ can include pneumonia, encephalitis, permanent pigmentation changes, skin scarring or bacterial superinfection at the site of the rash, hospitalization and, rarely, death. Shingles on the face can result in hearing or vision loss (3). In addition to being more likely to have severe, long-lasting rash, developing disseminated HZ and being at risk for re-developing shingles; immunocompromised individuals are more likely to experience complications and require hospitalization. Oral antiviral medications; such as acyclovir, valacyclovir and famciclovir; can be effective in shortening the length and severity of the rash when started within 72 hours of rash appearance but do not prevent pain or the development of PHN (1,3). Pain medications can help manage severe pain and topical products such as wet dressings and lotions may help relieve itching. PHN is challenging to treat and many patients do not experience adequate pain relief despite pharmacotherapy.

Vaccinating against HZ is the most effective way to prevent shingles and associated complications, including PHN (2,3). The first HZ vaccine; Zostavax®, or zoster vaccine live ZVL; was approved by the U.S. Food and Drug Administration in 2006 but is no longer available for use in the U.S. as of November 2020.3 The effectiveness of ZVL in preventing HZ was 70% in individuals aged 50-59 years, 64% in those aged 60-69 years and 38% in those over the age of 70 (2). A newer HZ vaccine; Shingrix®. or recombinant zoster vaccine RZV; was approved by the FDA in October 2017 for the prevention of shingles in adults aged 50 and older. (5). Unlike ZVL, RZV is an inactivated vaccine comprised of VZV glycoprotein E, or gE, and an adjuvant suspension referred to as AS01B (5). Required for viral replication, gE is found on the surface of cells infected with VZV. The role of the adjuvant is to stimulate and induce a higher gE-specific, cell-mediated immune response. ZVL does not contain preservatives (5).

The Advisory Committee on Immunization Practices recommends RZV for the prevention of HZ in immunocompetent adults aged 50 years or older (2). RZV is also FDA approved for adults aged 18 years and older who are or will be at increased risk of HZ due to immunodeficiency or immunosuppression caused by known disease or therapy (5). Testing for varicella antibody prior to or after administration is not required (3). RZV has not been evaluated in persons who are VZV-seronegative and the vaccine is not indicated for the prevention of chickenpox (varicella) (5). RZV is administered intramuscularly as a two-dose series at 0.5 mL each and is spaced two to six months apart. In clinical trials, two doses of RZV were 97% effective at preventing shingles and 91% effective in preventing PHN in adults aged 50 to 69. In adults 70 years or older, two doses of RZV were 91% effective in preventing shingles and 89% effective in preventing PHN, with protection continuing above 85% for at least the first four years after vaccination. (2,5). RZV is contraindicated in individuals who have had an anaphylactic reaction to any component of the vaccine or a previous dose. RZV should not be administered during an acute episode of HZ and is not recommended for use during pregnancy, in women who are breastfeeding or in severely compromised individuals as data to support use in these patient populations are lacking (2,5). While mild illness is not a contraindication to shingles vaccination, vaccination visits for patients with suspected or confirmed COVID-19, regardless of symptoms, should be postponed to avoid COVID-19 exposure (3). RZV can be administered concomitantly with other adult vaccines including influenza and pneumococcal vaccines at different anatomical sites (3,5). The ACIP recommends those who previously received ZVL also receive the two-dose series of RZV at least two months after ZVL (2). Common RZV adverse effects include pain, redness, and swelling at the injection site as well as muscle pain, tiredness, headache, shivering, fever and upset stomach. An increased risk of Guillain-Barré syndrome has been reported during the 42 days following vaccination (5).

RZV offers strong protection against shingles and PHN. Given the increased risk of morbidity, mortality and disability, as well as the significant economic and public health burden caused by HZ and PHN, all adults aged 50 or older should be counseled to receive and complete the RZV two-dose vaccine series.

References:

1. Cohen JL. Clinical practice: herpes zoster. N Engl J Med 2013;369(3):255-263.

2. Dooling KL, Guo A, Patel M, et al. Recommendations of the Advisory Committee on Immunization Practices for use of herpes zoster vaccines. January 26, 2018. Morbidiy and Mortality Weekly Report (MMWR), 67(3):103-108. Available at: https://www.cdc.gov/mmwr/volumes/67/ wr/mm6703a5.htm. Accessed: September 28, 2021.

3. Centers for Disease Control and Prevention (CDC). Shingles (herpes zoster). October 5, 2020. Available at: https://www.cdc.gov/shingles/. Accessed: September 28, 2021.

4. FamuyiroT, Smith ST, Raji M. Making the case for universal herpes zoster vaccination in older adults. Ann Longterm Care 2018;26(2):27-31.