Australian Herpes Management Forum

Herpes Zoster Vaccine

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Prof Anthony Cunningham

Vaccine

The biological rationale for the vaccine is to boost VZV cell-mediated immunity through immunisation as there is an increasing incidence of HZ in older adults probably due to the decline in VZV cell-mediated immunity with advancing age.

Zostavax is derived from the same VZV vaccine strain (Oka/Merck) as the licensed varicella (chickenpox) vaccine, Varivax, but is of higher potency (on average, at least 14 times greater). The higher viral titre in Zostavax is required to elicit a boost the cell mediates in immune response in adults. In those people who developed HZ despite vaccination, the severity of pain associated with the episode was also reduced.

In the United States Shingles Prevention Study (SPS), a double-blind, placebo-controlled, multicentre trial involving 38 546 participants aged 60 years or over, a live, attenuated, Oka/Merck strain, VZV vaccine (containing a viral titre 14 times higher than the current varicella vaccine) significantly altered the natural history of latent VZV, preventing HZ in the “young” old (60–69 years) and either preventing or attenuating HZ in older participants. Overall, the vaccine reduced the burden of illness from HZ by 61.1% (P < 0.001) and reduced its incidence by 51.3% (P < 0.001). The duration of pain and discomfort among participants with confirmed HZ was significantly shorter in the vaccine group (21 days v 24 days; P = 0.03) and the incidence of PHN was reduced by 66.5% (P < 0.001).

Role of a live vaccine for the prevention of herpes zoster

As the only vaccine able to prevent the clinical recurrence of a pre-existing latent viral infection (and which does not induce herd immunity), Zostavax is unique for National Immunisation Program.

The vaccine (Zostavax) is currently indicated in Australia for the prevention of HZ in individuals 50 years and older, and for the prevention of HZ and PHN and reduction of acute and chronic zoster-associated pain in individuals aged 60 years and older.

Age at vaccination

The duration of the vaccine’s effect is not yet known, early vaccination may increase the likelihood that a booster dose is required in later years. Vaccination at age 60 years as part of a national program will be convenient, as the vaccine can be given concomitantly with the influenza and pneumococcal vaccines, and still cover most elderly individuals at risk.

Zostavax is also licensed for use in people 50-59 years of age based on a study that demonstrated similar immunogenicity in this age group compared with those >60 years of age. However there have not yet been efficacy studies of Zostavax in people <60 years of age.

Therefore routine population-based use of zoster vaccine in people aged 50-59 years has not yet been recommended.

Safety

The Shingles Prevention Study, together with other smaller studies, demonstrated that Zostavax is safe and generally well tolerated among adults >50 years of age. In the SPS, the most common adverse events were injection site reactions, with Zostavax more likely to result in erythema, pain, and swelling at the injection site compared with placebo (48% vs 17% respectively). Varicella-like rashes at the injection site were also more common; however, varicella-like rash not localised to the injection site did not occur more often. Varicella- or zoster-like rashes that were PCR positive for VZV were mostly due to wild-type VZV. The incidence of fever was no greater in vaccine recipients; however, the rate of vaccine-related systemic systems symptoms was greater in vaccinees (Zostavax 6.3% vs placebo 4.9%), with the most frequently reported systemic symptoms being headache and fatigue.

Use in immunosuppression

Live vaccines are usually contraindicated in immunosuppressed people. Clinicians should refer to the Australian immunisation handbook for guidelines on administering live virus vaccines to this patient group. In patients for whom HZ vaccination is contraindicated, the priority should be early diagnosis of HZ and prompt treatment with antiviral agents. The effectiveness of a “killed” vaccine for use in immunosuppressed individuals is currently being explored.

The safety and efficacy of the zoster vaccine has not yet been established in adults with HIV, with or without evidence of immunosuppression.

Immunocompetent individuals aged 60 years or less who are VZV seropositive and expect to become immunocompromised in the future (e.g., future organ transplant, before chemotherapy, early HIV) may benefit from HZ vaccination. The efficacy of the vaccine and its durability following the subsequent immunosuppression are, however, unknown. People who have been given immunosuppressive therapy but are in remission, are between rounds of chemotherapy or are having a break from immunosuppressive therapy, may also benefit from the vaccine. Research is ongoing in this area.

Vaccination of varicella zoster virus-naïve individuals

The epidemiology of HZ in Australia is well described; clinicians can assume that any long-term resident of Australia is VZV immune. The immune status of foreign-born individuals cannot be assumed; VZV exposure has been reported to be as low as 40%–50% in some tropical countries. However, the zoster vaccine was safe when given to 125 subjects who had never had primary varicella infection.

Transmission of vaccine virus

Experience with varicella vaccines suggests it is unlikely that the zoster vaccine strain will be transmitted between people who have been vaccinated and susceptible contacts. Although a much higher viral titre is used for zoster prevention, most individuals will have residual specific antibody and (memory) T-cells to varicella vaccines. The risk of transmitting the attenuated vaccine virus to a susceptible individual should be weighed against the risk of developing natural zoster that could be transmitted to a susceptible individual. It is expected that the attenuated vaccine virus would respond well to antiviral treatment.

Individuals with prior herpes zoster

The use and safety of vaccinating an individual who has had HZ in the distant past (estimated to be about 15% of the target population) is currently being studied. The time interval is likely to be important; the rationale behind vaccinating a 70-year-old following an episode of HZ at age 63 is not compelling, but a strong argument could be made for vaccinating the same individual if the HZ occurred at the age of 40. The US Advisory Committee on Immunisation Practices currently recommends vaccination regardless of prior history of HZ.

Research directions and conclusion

Future research will address the uncertainty about the vaccine’s safety and efficacy in currently unstudied clinical settings (e.g. immunosuppressed individuals, younger age groups) and show whether a booster dose is required.

 

Document Information

Created: June 2008