Vaccines for preventing herpes zoster in older adults - PubMed (original) (raw)
Review
Vaccines for preventing herpes zoster in older adults
Juliana de Oliveira Gomes et al. Cochrane Database Syst Rev. 2023.
Abstract
Background: Herpes zoster, commonly known as shingles, is a neurocutaneous disease caused by the reactivation of the virus that causes varicella (chickenpox). After resolution of the varicella episode, the virus can remain latent in the sensitive dorsal ganglia of the spine. Years later, with declining immunity, the varicella zoster virus (VZV) can reactivate and cause herpes zoster, an extremely painful condition that can last many weeks or months and significantly compromise the quality of life of the affected person. The natural process of ageing is associated with a reduction in cellular immunity, and this predisposes older adults to herpes zoster. Vaccination with an attenuated form of the VZV activates specific T-cell production avoiding viral reactivation. Two types of herpes zoster vaccines are currently available. One of them is the single-dose live attenuated zoster vaccine (LZV), which contains the same live attenuated virus used in the chickenpox vaccine, but it has over 14-fold more plaque-forming units of the attenuated virus per dose. The other is the recombinant zoster vaccine (RZV) which does not contain the live attenuated virus, but rather a small fraction of the virus that cannot replicate but can boost immunogenicity. The recommended schedule for the RZV is two doses two months apart. This is an update of a Cochrane Review first published in 2010, and updated in 2012, 2016, and 2019.
Objectives: To evaluate the effectiveness and safety of vaccination for preventing herpes zoster in older adults.
Search methods: For this 2022 update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL 2022, Issue 10), MEDLINE (1948 to October 2022), Embase (2010 to October 2022), CINAHL (1981 to October 2022), LILACS (1982 to October 2022), and three trial registries.
Selection criteria: We included studies involving healthy older adults (mean age 60 years or older). We included randomised controlled trials (RCTs) or quasi-RCTs comparing zoster vaccine (any dose and potency) versus any other type of intervention (e.g. varicella vaccine, antiviral medication), placebo, or no intervention (no vaccine). Outcomes were cumulative incidence of herpes zoster, adverse events (death, serious adverse events, systemic reactions, or local reaction occurring at any time after vaccination), and dropouts.
Data collection and analysis: We used the standard methodological procedures expected by Cochrane.
Main results: We included two new studies involving 1736 participants in this update. The review now includes a total of 26 studies involving 90,259 healthy older adults with a mean age of 63.7 years. Only three studies assessed the cumulative incidence of herpes zoster in groups that received vaccines versus placebo. Most studies were conducted in high-income countries in Europe and North America and included healthy Caucasians (understood to be white participants) aged 60 years or over with no immunosuppressive comorbidities. Two studies were conducted in Japan and one study was conducted in the Republic of Korea. Sixteen studies used LZV. Ten studies tested an RZV. The overall certainty of the evidence was moderate, which indicates that the intervention probably works. Most data for the primary outcome (cumulative incidence of herpes zoster) and secondary outcomes (adverse events and dropouts) came from studies that had a low risk of bias and included a large number of participants. The cumulative incidence of herpes zoster at up to three years of follow-up was lower in participants who received the LZV (one dose subcutaneously) than in those who received placebo (risk ratio (RR) 0.49, 95% confidence interval (CI) 0.43 to 0.56; risk difference (RD) 2%; number needed to treat for an additional beneficial outcome (NNTB) 50; moderate-certainty evidence) in the largest study, which included 38,546 participants. There were no differences between the vaccinated and placebo groups for serious adverse events (RR 1.08, 95% CI 0.95 to 1.21) or deaths (RR 1.01, 95% CI 0.92 to 1.11; moderate-certainty evidence). The vaccinated group had a higher cumulative incidence of one or more adverse events (RR 1.71, 95% CI 1.38 to 2.11; RD 23%; number needed to treat for an additional harmful outcome (NNTH) 4.3) and injection site adverse events (RR 3.73, 95% CI 1.93 to 7.21; RD 28%; NNTH 3.6; moderate-certainty evidence) of mild to moderate intensity. These data came from four studies with 6980 participants aged 60 years or older. Two studies (29,311 participants for safety evaluation and 22,022 participants for efficacy evaluation) compared RZV (two doses intramuscularly, two months apart) versus placebo. Participants who received the new vaccine had a lower cumulative incidence of herpes zoster at 3.2 years follow-up (RR 0.08, 95% CI 0.03 to 0.23; RD 3%; NNTB 33; moderate-certainty evidence), probably indicating a favourable profile of the intervention. There were no differences between the vaccinated and placebo groups in cumulative incidence of serious adverse events (RR 0.97, 95% CI 0.91 to 1.03) or deaths (RR 0.94, 95% CI 0.84 to 1.04; moderate-certainty evidence). The vaccinated group had a higher cumulative incidence of adverse events, any systemic symptom (RR 2.23, 95% CI 2.12 to 2.34; RD 33%; NNTH 3.0), and any local symptom (RR 6.89, 95% CI 6.37 to 7.45; RD 67%; NNTH 1.5). Although most participants reported that their symptoms were of mild to moderate intensity, the risk of dropouts (participants not returning for the second dose, two months after the first dose) was higher in the vaccine group than in the placebo group (RR 1.25, 95% CI 1.13 to 1.39; RD 1%; NNTH 100, moderate-certainty evidence). Only one study reported funding from a non-commercial source (a university research foundation). All other included studies received funding from pharmaceutical companies. We did not conduct subgroup and sensitivity analyses AUTHORS' CONCLUSIONS: LZV (single dose) and RZV (two doses) are probably effective in preventing shingles disease for at least three years. To date, there are no data to recommend revaccination after receiving the basic schedule for each type of vaccine. Both vaccines produce systemic and injection site adverse events of mild to moderate intensity. The conclusions did not change in relation to the previous version of the systematic review.
Trial registration: ClinicalTrials.gov NCT03120364 NCT00886613 NCT01505647 NCT01777321 NCT03894969 NCT04334577 NCT02180295 NCT02526745 NCT03116594 NCT04091451 NCT04210752 NCT04869982 NCT05007041 NCT05047770 NCT05219253 NCT05245838.
Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Conflict of interest statement
Anna MZ Gagliardi has declared that they have no conflict of interest. Brenda NG Andriolo has declared that they have no conflict of interest. Maria R Torloni has declared that they have no conflict of interest. Juliana O Gomes has declared that they have no conflict of interest. Regis B Andriolo has declared that they have no conflict of interest. Eduardo C Cruz has declared that they have no conflict of interest.
Figures
1
Study flow diagram 2022 update.
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
1.1. Analysis
Comparison 1: Live zoster vaccine versus placebo, Outcome 1: Cumulative incidence of herpes zoster
1.2. Analysis
Comparison 1: Live zoster vaccine versus placebo, Outcome 2: Participants with adverse events
1.3. Analysis
Comparison 1: Live zoster vaccine versus placebo, Outcome 3: Duration in days of adverse events
1.4. Analysis
Comparison 1: Live zoster vaccine versus placebo, Outcome 4: Dropouts
1.5. Analysis
Comparison 1: Live zoster vaccine versus placebo, Outcome 5: Participants with no follow‐up
2.1. Analysis
Comparison 2: Recombinant zoster vaccine versus placebo, Outcome 1: Cumulative incidence of herpes zoster at least 3.2 years follow‐up
2.2. Analysis
Comparison 2: Recombinant zoster vaccine versus placebo, Outcome 2: Incidence of herpes zoster at least 4 years follow‐up
2.3. Analysis
Comparison 2: Recombinant zoster vaccine versus placebo, Outcome 3: Participants with adverse events
2.4. Analysis
Comparison 2: Recombinant zoster vaccine versus placebo, Outcome 4: Dropouts
Update of
- Vaccines for preventing herpes zoster in older adults.
Gagliardi AM, Andriolo BN, Torloni MR, Soares BG, de Oliveira Gomes J, Andriolo RB, Canteiro Cruz E. Gagliardi AM, et al. Cochrane Database Syst Rev. 2019 Nov 7;2019(11):CD008858. doi: 10.1002/14651858.CD008858.pub4. Cochrane Database Syst Rev. 2019. PMID: 31696946 Free PMC article. Updated.
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References to studies excluded from this review
Hayward 1994 {published data only}
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Irwin 2007 {published data only}
Johnson 2022 {published data only}
Kerzner 2007 {published data only}
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MacIntyre 2010 {published data only}
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NCT03894969 {unpublished data only}2018‐002977‐24
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Patterson‐Bartlett 2007 {published data only}
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Weinberg 2018 {published data only}
References to studies awaiting assessment
NCT03314103 {unpublished data only}
- NCT03314103. A multi-center, randomized, double-blinded, phase 3 trial to evaluate the efficacy against herpes zoster of a live attenuated varicella-zoster virus vaccine in adults over 40 years of age. clinicaltrials.gov/ct2/show/NCT03314103 (first received 19 October 2017).
NCT04334577 {unpublished data only}
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References to ongoing studies
NCT02180295 {unpublished data only}
- NCT02180295. A lot-to-lot consistency study to evaluate safety, tolerability, and immunogenicity of inactivated varicella zoster virus (VZV) vaccine in healthy adults (V212-014). clinicaltrials.gov/ct2/show/NCT02180295 (first received 2 July 2014).
NCT02526745 {unpublished data only}
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NCT03116594 {unpublished data only}
- NCT03116594. Immunogenicity and safety of two lots of NBP608 compared to Zostavax in healthy adult aged 50 and over. clinicaltrials.gov/ct2/show/NCT03116594 (first received 17 April 2017).
NCT04091451 {unpublished data only}
- NCT04091451. A safety and immunogenicity study of GSK Biologicals' herpes zoster subunit vaccine (HZ/su) GSK1437173A on a two-dose schedule in adults ≥ 50 years of age with a prior episode of herpes zoster. clinicaltrials.gov (first received 19 April 2017).
NCT04210752 {unpublished data only}
- NCT04210752. A phase 1, randomised, activator-controlled, double-blind, parallel study to assess the safety, tolerability and explore the immunogenicity of EG-HZ in healthy adult volunteers. clinicaltrials.gov/ct2/show/NCT04210752 (first received 24 February 2020).
NCT04869982 {unpublished data only}
- NCT04869982. A phase IV, randomized, observer-blind, placebo-controlled, multi-center study to assess the prophylactic efficacy against herpes zoster, immunogenicity and safety of Shingrix when administered intramuscularly on a 2-dose schedule in Chinese adults aged 50 years and older. clinicaltrials.gov/study/NCT04869982 (first received 3 May 2021).
NCT05007041 {unpublished data only}
- NCT05007041. Safety of simultaneous vaccination with zoster vaccine recombinant (RZV) and quadrivalent adjuvanted inactivated influenza vaccine (aIIV4). clinicaltrials.gov/ct2/show/NCT05007041 (first received 21 September 2021).
NCT05047770 {unpublished data only}
- NCT05047770. A phase III, randomized, open-label, controlled, multicenter study to evaluate the immune response and safety of both herpes zoster subunit vaccine in healthy adults aged 50 years and older AND the influenza virus vaccine in healthy adults aged 18 years and older when administered sequentially or coadministered with mRNA-1273 booster vaccination. clinicaltrials.gov/ct2/show/NCT05047770 (first received 17 September 2021).
NCT05219253 {unpublished data only}
- NCT05219253. A phase 3, randomised, observer-blind, placebo-controlled, multi-centre study to evaluate the immune response and safety of the herpes zoster subunit vaccine when administered intramuscularly on a 2-dose schedule in adults aged 50 years and older in India. clinicaltrials.gov/ct2/show/NCT05219253 (first received 2 February 2018).
NCT05245838 {unpublished data only}
- NCT05245838. A phase 1 randomized, subject-blinded, active-controlled, dose escalation, multicenter trial to evaluate the safety, tolerability, and immunogenicity of an investigational herpes zoster vaccine (Z-1018) compared to Shingrix® in healthy adult volunteers between the ages of 50 and 69 years. clinicaltrials.gov/ct2/show/NCT05245838 (first received 18 February 2022).
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