More opportunities for shingles protection with recombinant vaccine

In the past few months, New Zealand has been discontinuing the live attenuated herpes zoster vaccine (Zostavax) on the National Immunisation Schedule and replacing it with an adjuvanted recombinant subunit zoster vaccine (Shingrix). This article investigates why a shingles vaccine is important, the differences between these two vaccines and the advantages of changing vaccine.

Annually, there are approximately 500 zosterassociated hospitalisations in New Zealand

Commonly known as shingles (from Latin “cingulum”, meaning belt/girdle), herpes zoster (zoster) is a painful condition that can interfere with daily activities for a few days to weeks. Varicella-zoster virus (VZV) is a highly contagious herpes virus commonly acquired in childhood, presenting as chickenpox/varicella. VZV persists in the sensory nerve ganglia for life, and suppression is maintained by the immune system.

Zoster complications occur in one in four people, with risk increasing with age. The severity often depends on which dermatome is infected. Cranial nerve infections can result in severe headache; facial paralysis; herpes zoster ophthalmicus (HZO) and other eye complications; and ear involvement, including vertigo, ear pain and deafness. If left untreated or severe, secondary bacterial infections result in hospitalisation and sepsis. Annually, there are approximately 500 zoster-associated hospitalisations in New Zealand.

Chronic neuropathic pain, known as post-herpetic neuralgia (PHN), can last several months or even years, affecting quality of life, physical and emotional wellbeing, and in older people, resulting in loss of independence. PHN occurs in about one-third of people, increasing to half of those aged over 70. Antiviral medication taken within three days of symptom onset can reduce complications, but many people do not seek medical care so soon unless in severe discomfort.

Zoster can occur at any age. The incidence is greatest at age 65–80, increasing with age from 50 due to immunosenescence. It is also prevalent in younger people who are immunocompromised due to medical conditions or treatments. Cases have been increasing in recent years and most recently associated with COVID-19.

Vaccines boost VZV immunity to keep the virus suppressed, thereby reducing severity and risk of complications. Funded since April 2018, the live attenuated zoster vaccine, Zostavax, was used to immunise immunocompetent adults at age 65. There are two large drawbacks of this vaccine – it is contraindicated for those with moderate to severe immunocompromise, and it was not licensed for those under the age of 50. This meant that a large proportion of those at increased risk of zoster could not be protected.

In January 2020, an adjuvanted recombinant subunit zoster vaccine, Shingrix, was approved for use in New Zealand from the age of 50; in June 2022, the approval was expanded to those aged from 18 years at increased risk of zoster; and it was funded from September 2022 to replace Zostavax (once the stocks had been used) at age 65 only.

Shingrix contains recombinant glycoprotein E – an abundant VZV surface glycoprotein – and a proprietary saponin-based adjuvant, designated AS01B. It is designed to specifically induce cellular and humoral immunity against VZV glycoprotein E. For more information about the adjuvant, see “Vaccines”, New Zealand Doctor, 3 August.

Two doses, given intramuscularly two to six months apart, are highly efficacious, even with increasing age. In clinical trials, vaccine efficacy against zoster and PHN was approximately 90 per cent from age 50 and 70, including in individuals with pre-existing medical conditions (hypertension, diabetes, coronary heart disease, respiratory disorders).

Furthermore, after an initial decline during the first four to six years after vaccination with Shingrix, efficacy against zoster remains at over 70 per cent for up to 10 years (see figure). Efficacy of 68 to 91 per cent against zoster, PHN and zoster hospitalisation has also been shown in individuals aged from 18 who are severely immunocompromised (eg, stem cell transplant, renal transplant, immune-mediated inflammatory diseases and haematological malignancy).

Effectiveness of 70 and 76 per cent against zoster and PHN, respectively, was shown in US Medicare beneficiaries aged over 65 (based on suspected zoster cases, rather than confirmed cases as used in clinical trials).

Associated with increased immunogenicity, the adjuvant can also increase reactogenicity. Activation of an innate proinflammatory response leads to local reactions, such as injection-site pain (two-thirds of recipients) and redness/swelling (one-third of recipients), and systemic responses, such as headaches (two in five) and mild fever (one in five).

These adverse reactions are manageable, but it is still important to alert those receiving the vaccine to anticipate these responses. As with the COVID-19 vaccines, it is advisable to ensure frail, older people are well hydrated and monitored for at least 24 hours after vaccination.

Still under investigation, rare but potential associations with Guillain–Barré Syndrome and recurrence of HZO have been reported following Shingrix vaccination. Report any adverse events of concern to the Centre for Adverse Reactions Monitoring with as much detail (dose spacing, health, age, sex, etc) as possible.

Currently, two doses of Shingrix are funded for those aged 65. The two doses are given intramuscularly two to six months apart. For those who turn 66 between the first and second dose, both doses are funded, but neither dose is funded if aged 66 or over when the first dose is given. (Eligibility is subject to change, so check the current Pharmac schedule.)

Unlike Zostavax, Shingrix can be given to individuals who are severely immunocompromised as it is not a live vaccine. Serology for VZV immunity is not required for any groups because there are no safety concerns about giving this vaccine to individuals who are VZV naive. It is not yet known if Shingrix protects against varicella because VZV-naive individuals were excluded from clinical trials.

Individuals aged 50–64 or over 65 are also recommended to receive Shingrix (unfunded). Consider Shingrix for those who have previously had zoster or have medical conditions that increase their risk. Certain individuals aged from 18 are at increased risk of zoster, particularly those who are severely immunocompromised (see the Immunisation Handbook 2020; tinyurl.com/ImmHandbook20).

Individuals who have previously received Zostavax may also choose to receive Shingrix. Since both a previous zoster episode and previous vaccination with Zostavax are likely to have boosted immunity temporarily, allow 12 months before receiving Shingrix.

Mary Nowlan is a senior advisor at the Immunisation Advisory Centre