A New and Improved Vaccine to Help Prevent Shingles

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Sheila Krishna, M.D.

Shingles, or herpes zoster, is a common condition in which latent varicella zoster virus (VZV) is reactivated in the nerves and skin and creates a painful rash. There are approximately 1 million cases of shingles in the United States each year.  One in three people can expect to have an episode of shingles during their lifetime, with the number rising to one in two for those over the age of 85.

 

Varicella zoster virus, also known as the chickenpox virus, typically infects people, or is introduced with the chicken pox vaccine, in childhood, and remains dormant (latent) in the body’s nerve cells. Over 90% of the adult US population has had exposure to the  varicella zoster virus, but by age 55, 30-40% of people have lost their immunity to the virus.  The virus can get reactivated in the form of shingles when the immune system is no longer able to keep the virus in check.

 

Shingles can occur at any time in life, but it typically does so during periods of stress, immunosuppression, or most commonly with advancing age. Shingles usually presents as clusters of burning, painful blisters on top of inflamed patches of skin.  It typically occurs on one side of the body in a  pattern following the course of the underlying nerve. The most common sites for shingles are the torso, arms, and face.  The rash can take up to a month to heal.  While shingles is typically limited to one part of the body, the infection can rarely disseminate to the entire body and central nervous system, lungs, or other internal organs. This typically only  occurs in people with low immune function, such as those receiving chemotherapy or with specific immune deficiency syndromes.

 

Shingles that is limited to the skin will typically resolve without treatment. However, a common complication is the development of postherpetic neuralgia (PHN), PHN is more common in people who develop shingles after the age of 80, and manifests as stabbing, shooting pain that can greatly affect quality of life and can become chronic. PHN is the the most common complication of shingles and occurs in 10-18% of shingles cases. Due to the high incidence of PHN, patients with shingles are often offered antiviral therapy with drugs such as famciclovir-Famvir- or valacyclovir-Valtrex-, particularly within the first 48-72 hours after development of the rash.  Early treatment can also help with the acute pain and expedite healing of the rash.

 

Despite the use of antiviral medication, it remains common for people with shingles  to develop post-herpetic neuralgia. As a result, vaccination has been explored for the past 15 years in order to decrease the incidence of shingles and post-herpetic neuralgia. In 2006, the first shingles vaccine was approved by the Food and Drug Administration, under the trade name Zostavax, for adults over the age of 50.

 

Vaccines are generally prepared as live or killed preparations of the bacteria or virus they intend to prevent. For example, the annual influenza vaccine is a killed viral preparation. In contrast, vaccines given for measles, mumps and rubella are live vaccines. Zostavax is a live vaccine, meaning it is made of live zoster virus. The virus is modified to be weaker than a true infection, but strong enough to allow the body to create an immune response.

 

Zostavax is moderately effective and reduces the rate of shingles by 50%. Importantly, it also reduces the incidence of PHN by almost 70%. It is a single dose vaccine and can be administered to any person  with a competent immune system. However, its effectiveness seems to decrease in patients over the age of 70, and it cannot be used in immunocompromised patients, who cannot tolerate live virus vaccines.

 

In response to the need for a more effective vaccine for older people and immunocompromised patients, a new shingles vaccine named Shingrix was developed and approved by the FDA in 2017. This new vaccine is known as a recombinant vaccine. It does not contain live virus, and can thus be used in a wider range of individuals.

 

Two pivotal studies were done to evaluate the efficacy of this new vaccine  Both trials showed that the vaccine was highly effective at  preventing shingles. When the study data were pooled together, the vaccine had an overall efficacy of 91.3% against shingles and an 88.8% efficacy against postherpetic neuralgia. Finally, these studies were conducted with 4 years of follow up, to ensure that the vaccine effects were long lasting and sustained.

 

Two doses of vaccine were required to achieve these results. The second dose was given within 2-6 months of the first dose to provide a robust immune response. The vaccine was not studied in pregnant or breastfeeding women and therefore is not recommended for this group. The vaccine was also studied in the context of other common vaccines and found specifically to be safe when given along with the annual influenza vaccine.

 

Shingrix was also studied in patients who had already been given Zostavax. In a small study, it was shown that the new vaccine was able to elicit immune responses in patients given the older vaccine in the past 5 years. There were also no safety differences and no differences in side effects.

 

Common side effects of the Shingrix vaccine are injection site pain redness and swelling, which is similar to many vaccines. Other potential side effects include muscle pain, headaches, fevers, and gastrointestinal upset in 20-40% of patients. This does represent a slightly higher risk of side effects as compared to the older vaccine. This could be attributable to the more robust immune response that it elicits.

 

Based on these findings, the CDC made the following recommendations in 2017 regarding the use of the Shingrix vaccine:

1. Recombinant zoster vaccine (Shingrix) is recommended for the prevention of herpes zoster and related complications for immunocompetent adults aged ≥50 years.
2. Shingrix is recommended for the prevention of herpes zoster and related complications for immunocompetent adults who previously received Zostavax
3. Shingrix is preferred over Zostavax for the prevention of herpes zoster and related complications.

The CDC also made note of special populations and the role of Shingrix in these groups. For those with a past history of shingles, the CDC recommended Shingrix to prevent possible recurrence. However, the vaccine should not be given if a patient is actively experiencing shingles. For patients with medical conditions such as diabetes, heart, or lung disease, the vaccine should be given. For immunocompromised patients, the vaccine should also be given. Lastly, for those who have never had chickenpox,, vaccination for primary chickenpox should be performed, as opposed to the newer vaccines for prevention of shingles.

 

In summary, the development of the Shingrix vaccine represents a major advancement in the management of herpes zoster and post herpetic neuralgia. With excellent efficacy for people in a wide age range of 50 to 80, and older, it holds great promise for the reduction of shingles cases and the chronic pain that often follows.

 

The vaccine will continue to undergo post approval research and real world study, and its use will continue to be refined for specific populations and clinical scenarios. Specific questions that remain to be answered include the safety and efficacy of Shingrix in immunocompromised patients, adherence to the 2 dose schedule, and short and long term effectiveness outside of clinical trials. At this time, for individuals older than 50 years of age with healthy immune systems, the new Shingrix vaccine represents an excellent opportunity to reduce the risk of shingles and its complications.

 

References

Cunningham AL, Lal H, Kovac M, et al, for the ZOE-70 Study Group. Efficacy of the herpes zoster subunit vaccine in adults 70 years of age or older. N Engl J Med. 2016;375(11):1019-1032.

Lal H, Cunningham AL, Godeaux O, et al, for the ZOE-50 Study Group. Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults. N Engl J Med. 2015;372(22):2087-2096.

Centers for Disease Control and Prevention. Recommendations of the Advisory Committee on Immunization Practices for use of herpes zoster vaccines. MMWR. 2018;67(3):103-108.

Grupping K, Campora L, Douha M, et al. Immunogenicity and safety of the HZ/su adjuvanted herpes zoster subunit vaccine in adults previously vaccinated with a live attenuated herpes zostervaccine. J Infect Dis. 2017;216(11):1343-1351.

Chlibek R, Smetana J, Pauksens K, et al. Safety and immunogenicity of three different formulations of an adjuvanted varicella-zoster virus subunit candidate vaccine in older adults: a phase II, randomized, controlled study. Vaccine. 2014;32(15):1745-1753.

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