Key messages
Vaccines can prevent shingles in healthy older adults.
What is herpes zoster?
Herpes zoster is a reactivation of the varicella zoster virus. Varicella zoster virus causes chickenpox and can remain inactive in nerve cells for many years. The virus can reactivate, travel through the nerve to the skin, and produce blisters along the nerve path. This condition is called shingles (herpes zoster), and mostly affects people with low immunity, such as older people. Before blisters appear, symptoms may include itching, numbness, tingling, or local pain. Shingles causes nerve inflammation and severe pain that can affect quality of life. The incidence rate of herpes zoster ranges from 2.08 cases to 6.20 cases per 1000 person-years (i.e. the number of new cases per population at risk, in a given time period). This number is increasing, due in part to people living longer.
What did we want to find out?
We wanted to find out whether healthy older adults who receive the herpes zoster virus vaccine are less likely to develop this disease compared to healthy older adults who receive a 'fake vaccine' (i.e. a placebo, which is an injection that does not cause any effect related to herpes zoster). We also wanted to know if the vaccine, compared to the fake vaccine, caused any undesirable effects.
What did we do?
We looked for studies that investigated and compared healthy older adults (mean age of participants 60 years and older) who received the vaccine to protect against herpes zoster, to healthy older adults who received the fake vaccine.
We compared and summarised the findings, and assessed our confidence in the evidence based on study size, on how the data were presented, and on the risks of bias (the likelihood that features of the study design or conduct of the study will lead to wrong results).
What did we find?
This is an update of the systematic review, and we found two new studies, bringing the total to 26 included studies (90,259 participants). These studies tested two types of vaccines that have already been approved for use. Sixteen studies tested the live attenuated virus vaccine (LZV) and included 55,975 participants (single dose); 10 studies tested the recombinant zoster vaccine (RZV), and included 34,284 participants (two doses with one two-month interval between them).
All studies involved people who were outpatients. Most study participants were Caucasian (White race).
Main results
Vaccine effectiveness
LZV (single dose)
The participants who received LZV had a lower rate of shingles compared to those who received the fake vaccine. Therefore, LZV is probably effective since the certainty of the evidence was moderate. It would be necessary to vaccinate 50 healthy older adults with LVZ to prevent one episode of shingles.
RZV (two doses)
Vaccination with RZV is also probably effective (moderate-certainty evidence), and perhaps more effective than vaccination with LZV, since results show that it would be necessary to vaccinate 33 healthy older adults to prevent one episode of shingles.
Safety
Both vaccines are probably safe (moderate-certainty evidence) for unwanted effects.
In studies that tested RZV, which requires a second dose two months later, the dropout rate (number of persons who did not receive the second dose) was higher in the group that received the real vaccine than in the group that received the fake vaccine. This can be quantified in such a way that for every 100 healthy older adults vaccinated with two doses of the real vaccine, one older adult who received the first dose of this vaccine did not receive the second dose. The reactogenicity (side effects) of the first dose of the vaccine may have contributed to this behaviour.
Conclusion
LZV (single dose) and RZV (two doses) are probably effective in preventing shingles disease for at least three years. For both vaccines, the certainty of evidence was moderate in terms of efficacy and safety for at least three years.
What are the limitations of the evidence?
We have moderate-certainty evidence for all effectiveness and safety endpoints, based on studies that included a large number of healthy older adults aged 60 years or older.
How up-to-date is this evidence?
The evidence is current to 21 October 2022.
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.
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.
To evaluate the effectiveness and safety of vaccination for preventing herpes zoster in older adults.
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.
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.
We used the standard methodological procedures expected by Cochrane.
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