Vaccination can help prevent HZ and HZ-related postherpetic neuralgia.[31]de Oliveira Gomes J, Gagliardi AM, Andriolo BN, et al. Vaccines for preventing herpes zoster in older adults. Cochrane Database Syst Rev. 2023 Oct 2;10(10):CD008858.
http://www.ncbi.nlm.nih.gov/pubmed/37781954?tool=bestpractice.com
[32]Klein NP, Bartlett J, Fireman B, et al. Effectiveness of the live zoster vaccine during the 10 years following vaccination: real world cohort study using electronic health records. BMJ. 2023 Nov 8;383:e076321.
https://www.bmj.com/content/383/bmj-2023-076321.long
http://www.ncbi.nlm.nih.gov/pubmed/37940142?tool=bestpractice.com
[33]Zerbo O, Bartlett J, Fireman B, et al. Effectiveness of recombinant zoster vaccine against herpes zoster in a real-world setting. Ann Intern Med. 2024 Feb;177(2):189-95.
http://www.ncbi.nlm.nih.gov/pubmed/38190712?tool=bestpractice.com
Shingrix® is a recombinant zoster vaccine that contains varicella-zoster virus (VZV) glycoprotein E and the AS01B adjuvant system. Zostavax® is a lyophilized or freeze-dried preparation of the Oka/Merck strain of live, attenuated VZV.
Zostavax® was the first vaccine approved for use in adults ages ≥50 years for the prevention of HZ and HZ-related postherpetic neuralgia.[34]Sanford M, Keating GM. Zoster vaccine (Zostavax): a review of its use in preventing herpes zoster and postherpetic neuralgia in older adults. Drugs Aging. 2010 Feb 1;27(2):159-76.
http://www.ncbi.nlm.nih.gov/pubmed/20104941?tool=bestpractice.com
[35]US Food and Drug Administration. Vaccines, blood and biologics: Zostavax. Dec 2019 [internet publication].
https://www.fda.gov/vaccines-blood-biologics/vaccines/zostavax
[36]Chen N, Li Q, Zhang Y, et al. Vaccination for preventing postherpetic neuralgia. Cochrane Database Syst Rev. 2011 Mar 16;(3):CD007795.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD007795.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/21412911?tool=bestpractice.com
[37]Schmader KE, Levin MJ, Gnann JW Jr, et al. Efficacy, safety, and tolerability of herpes zoster vaccine in persons aged 50-59 years. Clin Infect Dis. 2012 Apr;54(7):922-8.
https://academic.oup.com/cid/article/54/7/922/299086
http://www.ncbi.nlm.nih.gov/pubmed/22291101?tool=bestpractice.com
In 2017 Shingrix® was approved by the Food and Drug Administration (FDA), also for adults ages ≥50 years. Following the FDA approval, the Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) recommend using Shingrix® in place of Zostavax® for preventing HZ and postherpetic neuralgia in people ages ≥50 years.[38]Dooling KL, Guo A, Patel M, et al. Recommendations of the Advisory Committee on Immunization Practices for use of herpes zoster vaccines. MMWR Morb Mortal Wkly Rep. 2018 Jan 26;67(3):103-8.
https://www.cdc.gov/mmwr/volumes/67/wr/mm6703a5.htm
http://www.ncbi.nlm.nih.gov/pubmed/29370152?tool=bestpractice.com
This represents a lowering of the recommended vaccination age from ≥60 years. The ACIP also recommended that all patients previously vaccinated with Zostavax® receive Shingrix® at least 2 months after their initial vaccination. Shingrix® requires 2 intramuscular doses to be administered 2 to 6 months apart, and has a substantially higher efficacy than Zostavax®, reducing HZ cases by 97%.[39]Lal H, Cunningham AL, Godeaux O, et al; ZOE-50 Study Group. Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults. N Engl J Med. 2015 May 28;372(22):2087-96.
https://www.nejm.org/doi/full/10.1056/NEJMoa1501184
http://www.ncbi.nlm.nih.gov/pubmed/25916341?tool=bestpractice.com
[40]Cunningham AL, Lal H, Kovac M, et al; ZOE-70 Study Group. Efficacy of the herpes zoster subunit vaccine in adults 70 years of age or older. N Engl J Med. 2016 Sep 15;375(11):1019-32.
https://www.nejm.org/doi/full/10.1056/NEJMoa1603800
http://www.ncbi.nlm.nih.gov/pubmed/27626517?tool=bestpractice.com
[41]Centers for Disease Control and Prevention. Adult immunization schedule by age. Recommendations for ages 19 years or older, United States, 2025. Nov 2024 [internet publication].
https://www.cdc.gov/vaccines/hcp/imz-schedules/adult-age.html
An analysis combining two large phase 3 trials of Shingrix® demonstrated that its efficacy against HZ-related complications was similar in adults aged ≥50 years and ≥70 years, and most of the reduction in HZ-related complications was driven by the reduction of HZ cases.[42]Kovac M, Lal H, Cunningham AL, et al. Complications of herpes zoster in immunocompetent older adults: incidence in vaccine and placebo groups in two large phase 3 trials. Vaccine. 2018 Mar 14;36(12):1537-41.
https://www.sciencedirect.com/science/article/pii/S0264410X18302032?via%3Dihub
http://www.ncbi.nlm.nih.gov/pubmed/29463421?tool=bestpractice.com
More importantly, the efficacy of Shingrix® declines only slightly after 7 years, remaining at >84%.[43]Boutry C, Hastie A, Diez-Domingo J, et al. The Adjuvanted Recombinant Zoster Vaccine Confers Long-Term Protection Against Herpes Zoster: Interim Results of an Extension Study of the Pivotal Phase 3 Clinical Trials ZOE-50 and ZOE-70. Clin Infect Dis. 2022 Apr 28;74(8):1459-67.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9049256
http://www.ncbi.nlm.nih.gov/pubmed/34283213?tool=bestpractice.com
However, efficacy data for the 2-dose series up to 10 years of follow-up are still under investigation. The efficacy of a single dose is also unknown, but studies suggest a single dose does not produce a robust immune response.[33]Zerbo O, Bartlett J, Fireman B, et al. Effectiveness of recombinant zoster vaccine against herpes zoster in a real-world setting. Ann Intern Med. 2024 Feb;177(2):189-95.
http://www.ncbi.nlm.nih.gov/pubmed/38190712?tool=bestpractice.com
[44]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 Mar 26;32(15):1745-53.
http://www.ncbi.nlm.nih.gov/pubmed/24508036?tool=bestpractice.com
[45]Parikh R, Singer D, Chmielewski-Yee E, et al. Effectiveness and safety of recombinant zoster vaccine: a review of real-world evidence. Hum Vaccin Immunother. 2023 Dec 15;19(3):2263979.
https://www.tandfonline.com/doi/full/10.1080/21645515.2023.2263979
http://www.ncbi.nlm.nih.gov/pubmed/37967254?tool=bestpractice.com
Therefore, physicians should try to ensure that patients receive both doses. Furthermore, it is important to complete the series within 2 to 6 months as indicated, because a series with doses 12 months apart has a lower immunogenicity.[46]Lal H, Poder A, Campora L, et al. Immunogenicity, reactogenicity and safety of 2 doses of an adjuvanted herpes zoster subunit vaccine administered 2, 6 or 12 months apart in older adults: results of a phase III, randomized, open-label, multicenter study. Vaccine. 2018 Jan 2;36(1):148-54.
https://www.sciencedirect.com/science/article/pii/S0264410X17315785?via%3Dihub
http://www.ncbi.nlm.nih.gov/pubmed/29174683?tool=bestpractice.com
There is currently no recommendation for Shingrix® in pregnancy; delaying vaccination until after pregnancy may be considered.[41]Centers for Disease Control and Prevention. Adult immunization schedule by age. Recommendations for ages 19 years or older, United States, 2025. Nov 2024 [internet publication].
https://www.cdc.gov/vaccines/hcp/imz-schedules/adult-age.html
Shingrix® prevents more cases of HZ but also causes more injection-site reactions than Zostavax®.[47]Tricco AC, Zarin W, Cardoso R, et al. Efficacy, effectiveness, and safety of herpes zoster vaccines in adults aged 50 and older: systematic review and network meta-analysis. BMJ. 2018 Oct 25;363:k4029.
https://www.bmj.com/content/363/bmj.k4029.long
http://www.ncbi.nlm.nih.gov/pubmed/30361202?tool=bestpractice.com
Grade 3 systemic vaccine reactions, defined as symptoms that prevent normal everyday activities, occur in up to 17% of vaccine recipients, and are more frequent after the second dose than the first.[39]Lal H, Cunningham AL, Godeaux O, et al; ZOE-50 Study Group. Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults. N Engl J Med. 2015 May 28;372(22):2087-96.
https://www.nejm.org/doi/full/10.1056/NEJMoa1501184
http://www.ncbi.nlm.nih.gov/pubmed/25916341?tool=bestpractice.com
A post-licensure safety surveillance 1 year after Shingrix® was introduced in the US found that safety data were consistent with the clinical trials.[48]Hesse EM, Shimabukuro TT, Su JR, et al. Postlicensure safety surveillance of recombinant zoster vaccine (Shingrix) - United States, October 2017 - June 2018. MMWR Morb Mortal Wkly Rep. 2019 Feb 1;68(4):91-4.
https://www.cdc.gov/mmwr/volumes/68/wr/mm6804a4.htm
http://www.ncbi.nlm.nih.gov/pubmed/30703077?tool=bestpractice.com
Shingrix® has been shown to be safe and immunogenic in patients previously vaccinated with Zostavax®.[49]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 zoster vaccine. J Infect Dis. 2017 Dec 12;216(11):1343-51.
https://academic.oup.com/jid/article/216/11/1343/4209275
http://www.ncbi.nlm.nih.gov/pubmed/2902912?tool=bestpractice.com
In addition, it can be safely coadministered with the influenza vaccine without interference with the immune response.[50]Schwarz TF, Aggarwal N, Moeckesch B, et al. Immunogenicity and safety of an adjuvanted herpes zoster subunit vaccine coadministered with seasonal influenza vaccine in adults aged 50 years or older. J Infect Dis. 2017 Dec 12;216(11):1352-61.
https://academic.oup.com/jid/article/216/11/1352/4191338
http://www.ncbi.nlm.nih.gov/pubmed/29029224?tool=bestpractice.com
Shingrix® has been shown to reduce the burden of illness of HZ and the severity of HZ-related pain and improve the patient's overall quality of life.[51]Curran D, Oostvogels L, Heineman T, et al; ZOE-50/70 Study Group. Quality of life impact of an adjuvanted recombinant zoster vaccine in adults aged 50 years and older. J Gerontol A Biol Sci Med Sci. 2019 Jul 12;74(8):1231-8.
https://academic.oup.com/biomedgerontology/article/74/8/1231/5046047
http://www.ncbi.nlm.nih.gov/pubmed/29955836?tool=bestpractice.com
An analysis of Medicare claims data has found an increased risk of Guillain-Barre syndrome (GBS) among people ages ≥65 years who received Shingrix®. Compared to Zostavax® recipients, older adults vaccinated with Shingrix® had a more than twofold higher risk of GBS, equivalent to an attributable risk of 6.47 cases per million doses. However, the risk-benefit balance for Shingrix® still supports its use.[52]Goud R, Lufkin B, Duffy J, et al. Risk of Guillain-Barré syndrome following recombinant zoster vaccine in medicare beneficiaries. JAMA Intern Med. 2021 Dec 1;181(12):1623-30.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8561433
http://www.ncbi.nlm.nih.gov/pubmed/34724025?tool=bestpractice.com
It is important to note that Zostavax® is administered as a single dose subcutaneously; and Shingrix® is administered as 2 doses (2 to 6 months apart in the general population, or 1 to 2 months apart in immunodeficient or immunosuppressed patients) intramuscularly. The need to mix two vaccine components combined with different storage requirements and a different route of administration from Zostavax® leads to a higher risk of errors when administering Shingrix® which has led to the CDC issuing a reminder to physicians.[53]Shimabukuro TT, Miller ER, Strikas RA, et al. Notes from the Field: vaccine administration errors involving recombinant zoster vaccine — United States, 2017–2018. MMWR Morb Mortal Wkly Rep. 2018 May 25;67(20):585-6.
https://www.cdc.gov/mmwr/volumes/67/wr/mm6720a4.htm
http://www.ncbi.nlm.nih.gov/pubmed/29795075?tool=bestpractice.com
Immunocompromised patients are at higher risk of HZ infection and vaccination is important.[54]Chen SY, Suaya JA, Li Q, et al. Incidence of herpes zoster in patients with altered immune function. Infection. 2014 Apr;42(2):325-34.
https://link.springer.com/article/10.1007/s15010-013-0550-8
http://www.ncbi.nlm.nih.gov/pubmed/24214127?tool=bestpractice.com
One randomized clinical trial of Shingrix® in adults who had undergone autologous hematopoietic stem cell transplantation found that a 2-dose course of the vaccine significantly reduced the incidence of HZ compared with placebo over a median follow-up of 21 months, with a vaccine efficacy of 68%.[55]Bastidas A, de la Serna J, El Idrissi M, et al; ZOE-HSCT Study Group Collaborators. Effect of recombinant zoster vaccine on incidence of herpes zoster after autologous stem cell transplantation: a randomized clinical trial. JAMA. 2019 Jul 9;322(2):123-33.
https://jamanetwork.com/journals/jama/fullarticle/2737683
http://www.ncbi.nlm.nih.gov/pubmed/31287523?tool=bestpractice.com
A post-hoc analysis of a phase 3 trial of Shingrix® in patients with hematologic malignancies showed an efficacy of 87% within 11 months of follow-up.[56]Dagnew AF, Ilhan O, Lee WS, et al. Immunogenicity and safety of the adjuvanted recombinant zoster vaccine in adults with haematological malignancies: a phase 3, randomised, clinical trial and post-hoc efficacy analysis. Lancet Infect Dis. 2019 Sep;19(9):988-1000.
https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(19)30163-X/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/31399377?tool=bestpractice.com
Other studies have shown that Shingrix® stimulates an immune response in kidney transplant recipients and patients with solid tumors.[57]Vink P, Ramon Torrell JM, Sanchez Fructuoso A, et al. Immunogenicity and Safety of the Adjuvanted Recombinant Zoster Vaccine in Chronically Immunosuppressed Adults Following Renal Transplant: A Phase 3, Randomized Clinical Trial. Clin Infect Dis. 2020 Jan 2;70(2):181-90.
https://academic.oup.com/cid/article/70/2/181/5370445
http://www.ncbi.nlm.nih.gov/pubmed/30843046?tool=bestpractice.com
[58]Vink P, Delgado Mingorance I, Maximiano Alonso C, et al. Immunogenicity and safety of the adjuvanted recombinant zoster vaccine in patients with solid tumors, vaccinated before or during chemotherapy: A randomized trial. Cancer. 2019 Apr 15;125(8):1301-12.
https://acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.31909
http://www.ncbi.nlm.nih.gov/pubmed/30707761?tool=bestpractice.com
In patients with HIV infection, two doses of Zostavax® were shown to be safe and immunogenic in persons with CD4 counts ≥200 cells/mm³.[59]Benson CA, Andersen JW, Macatangay BJC, et al. Safety and Immunogenicity of Zoster Vaccine Live in Human Immunodeficiency Virus-Infected Adults With CD4+ Cell Counts >200 Cells/mL Virologically Suppressed on Antiretroviral Therapy. Clin Infect Dis. 2018 Nov 13;67(11):1712-19.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6233680
http://www.ncbi.nlm.nih.gov/pubmed/29590326?tool=bestpractice.com
In a phase-1/2 randomized controlled trial, Shingrix® was shown to increase humoral and cell-mediated immunity among patients with CD4 counts <200 cells/mm³ and caused no vaccine-related severe adverse events.[60]Berkowitz EM, Moyle G, Stellbrink HJ, et al. Safety and immunogenicity of an adjuvanted herpes zoster subunit candidate vaccine in HIV-infected adults: a phase 1/2a randomized, placebo-controlled study. J Infect Dis. 2015 Apr 15;211(8):1279-87.
https://academic.oup.com/jid/article/211/8/1279/916271
http://www.ncbi.nlm.nih.gov/pubmed/25371534?tool=bestpractice.com
However, there are currently no phase 3 data for either Zostavax® or Shingrix® in patients with HIV. The US guideline for the prevention and treatment of opportunistic infections in adults with HIV recommends vaccination with Shingrix® for adults with HIV age ≥18 years, regardless of CD4 count.[10]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and Infectious Diseases Society of America. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: varicella-zoster virus. 2022 [internet publication].
https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/varicella-zoster
The vaccine should not be given during an acute episode of HZ and some experts would delay vaccination until the patient is virologically suppressed on antiretroviral therapy or until CD4 count recovery to maximize response to vaccine.[10]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and Infectious Diseases Society of America. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: varicella-zoster virus. 2022 [internet publication].
https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/varicella-zoster
The ACIP recommends Shingrix® in immunodeficient or immunosuppressed adults ages 19 and over.[61]Centers for Disease Control and Prevention. Morbidity and Mortality Weekly Report. Use of recombinant zoster vaccine in immunocompromised adults aged ≥ 19 Years: recommendations of the advisory committee on immunization practices — United States, 2022. Jan 2022 [internet publication].
https://www.cdc.gov/mmwr/volumes/71/wr/mm7103a2.htm
[62]Centers for Disease Control and Prevention. Clinical considerations for use of recombinant zoster vaccine (RZV, Shingrix) in immunocompromised adults aged ≥19 Years. Jan 2022 [internet publication].
https://www.cdc.gov/shingles/vaccination/immunocompromised-adults.html
Ideally, Shingrix® should be given before the patients become immunosuppressed or, otherwise, during the period when the immune response is strong (i.e., during periods of lower immunosuppression and stable disease).[63]Centers for Disease Control and Prevention. Shingles (Herpes Zoster). Feb 2022 [internet publication].
https://www.cdc.gov/shingles/index.html
In the US, Zostavax® is no longer commercially available; Shingrix® is the only vaccine available for the prevention of HZ.[63]Centers for Disease Control and Prevention. Shingles (Herpes Zoster). Feb 2022 [internet publication].
https://www.cdc.gov/shingles/index.html
In Europe, Shingrix® was granted marketing authorization for preventing HZ and post-herpetic neuralgia in persons ages ≥50 years in January 2018. In July 2020, the authorization was extended to include adults ages ≥18 years at increased risk of HZ. In the UK, from September 2023, Shingrix® will be offered to immunocompetent individuals from ages 60 years (in a phased implementation over a 10-year period starting with those turning 65 and 70 years of age) and to severely immunosuppressed individuals from ages 50 years, replacing Zostavax®.[64]UK Health Security Agency. Shingles vaccination: guidance for healthcare practitioners. Sep 2023 [internal publication].
https://www.gov.uk/government/publications/shingles-vaccination-guidance-for-healthcare-professionals