Volume 200 - Issue 5
Immunisation for herpes zoster: current status
Authors: Anthony L Cunningham, John C B Litt and C Raina MacIntyre
Med J Aust 2014; 200 (5): 243-244. || doi: 10.5694/mja14.00070
Published online: 17 March 2014
Published online: 17 March 2014
Herpes zoster is a painful, disabling condition so the recent development of preventive vaccines is welcome
Herpes zoster is a painful, disabling condition so the recent development of preventive vaccines is welcome
Herpes zoster, or shingles, can occur at virtually any age but is most common after the age of 50 years, and carries a lifetime risk of up to 50% in people living for 85 years or more. The incidence is about 3–4 per 1000 of the general Australian population, rising to about 10 per 1000 in those aged over 60 years and similar in other OECD countries.1,2 Herpes zoster is caused by the reactivation of the varicella zoster virus in the nerve cells of the dorsal root ganglion adjacent to the spinal cord.3 This reactivation occurs through waning of T cell immunity, also consistent with the increased incidence and severity in immunocompromised patients. However, the exact threshold and nature of T cell immunity required to prevent varicella viral reactivation is still unclear. This T cell immunity may be boosted by encounters with patients with chicken pox. Early studies showed promise in using live attenuated varicella vaccine to boost T cell immunity and prevent herpes zoster.4
A double-blind placebo-controlled shingles prevention study (SPS) was undertaken with a (14-fold) concentrated form of the live attenuated varicella (Oka strain) vaccine administered to 38 000 people in the United States over the age of 60 years.5 This landmark trial showed the vaccine to be both safe and efficacious, preventing herpes zoster in just over 50% of subjects, preventing postherpetic neuralgia (PHN) in 66% of subjects and also reducing the burden of illness (a measure of severity and duration of pain) in more than 60% of subjects in an average 3-year follow-up period. Efficacy in preventing shingles was significantly lower in people over the age of 70 years. Nevertheless the impact on the incidence of PHN was similar. Post-licensure studies of US patients receiving Zostavax (Zoster Vaccine Live) (Merck) using records from Medicare or other large health care organisations have confirmed the efficacy of the vaccine to be similar.6 Thus this vaccine showed two novel features: it is the first to successfully target T cell immunity and also to prevent viral reactivation.7
However, there are several important unanswered questions, including the duration of efficacy, safety in mildly immunocompromised patients and use in younger patients. The duration of efficacy has been addressed by short-term and long-term follow-up studies from the SPS. These studies show that efficacy wanes, probably over 5–8 years, so a booster at 10 years may be required. Although such a booster has been shown to be safe, this is yet to be implemented by licensing authorities in any country.7
New trials in younger patients showed good efficacy in subjects in the 50–59-years age group.8 However, so far, most countries have persisted with vaccination at age 60 years and, in the United Kingdom, at age 70 years. Simultaneous vaccination with Zostavax and influenza vaccine at age 60 years did not affect the efficacy of either vaccine, but this was not the case when Zostavax was administered with pneumococcal vaccine.9 Live attenuated vaccines such as Zostavax are contraindicated in severely immunocompromised patients, particularly those taking > 20 mg prednisone per day for 2 weeks, those with haematological malignancy or those receiving haemopoietic stem cell transplantation, or in those with HIV infection and immunosuppression (< 15% CD4 lymphocytes). The situation is not so well defined in patients who are mildly immunocompromised through receiving anti-tumour necrosis factor or other biologicals and in HIV-infected patients without severe immunocompromise. Although a recent small trial suggested that Zostavax may be safe in patients being treated with biologicals for autoimmune diseases, many specialists remain wary and further studies are required.10-12 Inactivated Zostavax is now undergoing Phase III trials in severely immunocompromised patients. There is now another type of zoster vaccine, consisting of a single recombinant varicella protein and antibody and T cell-boosting adjuvants, in the advanced stages of large Phase III trials.13
There has been much discussion about how childhood varicella and adult zoster vaccination may mesh in the future. In Australia, varicella vaccination has been part of the national immunisation program since 2005 and has resulted in significant reduction in circulating wild varicella virus. So far, with two doses, vaccine immunity is maintained for over 14 years.14 However, circulating virus boosts varicella virus T cell immunity and probably reduces the likelihood of clinical viral reactivation causing zoster.15-17 Thus, as suggested by Australian modelling studies,18 this program might lead to an increase in herpes zoster in the pre-2005 Australian population cohort, who still harbour wild type varicella virus in their dorsal root ganglia. There has been an increase in herpes zoster over the past 2 decades, which precedes the introduction of universal varicella vaccination.19 Any impact of varicella zoster virus vaccination is as yet uncertain.
Australia has an ageing population, and an important part of healthy ageing is preventing vaccine-preventable diseases. The increasing burden of herpes zoster with increasing age, the impact on quality of life of PHN, and potential prevention with an available vaccine that has waning immunity over time need to be considered for population health impact.
Competing interests
Anthony Cunningham and John Litt are on the Merck Global Advisory Board for Adult Vaccines and consult with bioCSL. Anthony Cunningham also consults with GlaxoSmithKline.
References
- Poletti P, Melegaro A, Ajelli M, et al. Perspectives on the impact of varicella immunization on herpes zoster. A model-based evaluation from three European countries. PLOS One 2013; 8: e60732. _ENREF_1
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- Steain M, Sutherland JP, Rodriguez M, et al. Analysis of T cell responses during active varicella-zoster virus reactivation in human ganglia. J Virol 2014; 88: 2704-2716. _ENREF_3
- Levin MJ, Murray M, Rotbart HA, et al. Immune response of elderly individuals to a live attenuated varicella vaccine. J Infect Dis 1992; 166: 253-259. _ENREF_4
- Oxman MN, Levin MJ, Johnson GR, et al. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med 2005; 352: 2271-2284. _ENREF_5
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- Levin MJ. Immune senescence and vaccines to prevent herpes zoster in older persons. Curr Opin Immunol 2012; 24: 494-500. _ENREF_7
- 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; 54: 922-928. _ENREF_9
- MacIntyre CR, Egerton T, McCaughey M, et al. Concomitant administration of zoster and pneumococcal vaccines in adults ≥ 60 years old. Hum Vaccin 2010; 6: 894-902. _ENREF_10
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- Australian Government Department of Health and Ageing. The Australian immunisation handbook: part 3 vaccination for special risk groups. http://www.immunise.health.gov.au/internet/immunise/publishing.nsf/Content/handbook10part3 (accessed Feb 2014).
- Zhang J, Xie F, Delzell E, et al. Association between vaccination for herpes zoster and risk of herpes zoster infection among older patients with selected immune-mediated diseases. JAMA 2012; 308: 43-49. _ENREF_13
- Leroux-Roels I, Leroux-Roels G, Clement F, et al. A phase 1/2 clinical trial evaluating safety and immunogenicity of a varicella zoster glycoprotein e subunit vaccine candidate in young and older adults. J Infect Dis 2012; 206: 1280-1290. 13
- Baxter R, Ray P, Tran TN, et al. Long-term effectiveness of varicella vaccine: a 14-year, prospective cohort study. Pediatrics 2013; 131: e1389-1396. 14
- Brisson M, Gay NJ, Edmunds WJ, Andrews NJ. Exposure to varicella boosts immunity to herpes-zoster: implications for mass vaccination against chickenpox. Vaccine 2002; 20: 2500-2507. _ENREF_16
- Carville KS, Riddell MA, Kelly HA. A decline in varicella but an uncertain impact on zoster following varicella vaccination in Victoria, Australia. Vaccine 2010; 28: 2532-2538. _ENREF_17
- Donahue JG, Kieke BA, Gargiullo PM, et al. Herpes zoster and exposure to the varicella zoster virus in an era of varicella vaccination. Am J Public Health 2010; 100: 1116-1122. _ENREF_18
- Gao Z, Gidding HF, Wood JG, MacIntyre CR. Modelling the impact of one-dose vs. two-dose vaccination regimens on the epidemiology of varicella zoster virus in Australia. Epidemiol Infect 2010; 138: 457-468. _ENREF_19
- Hales CM, Harpaz R, Joesoef MR, Bialek SR. Examination of links between herpes zoster incidence and childhood varicella vaccination. Ann Intern Med 2013; 159: 739-745. _ENREF_20
Provenance: Commissioned; externally peer reviewed.