Zoster or shingles, a dermatomal-vesicular infection, is caused by reactivation of latent varicella–zoster virus (VZV). Primary infection with VZV causes varicella. Zoster occurs following waning VZV cellular immunity and presents as a painful rash involving one or two adjacent dermatomes.
The rash is preceded by prodromal pain over the affected dermatome. It may be accompanied with headache, photophobia, malaise with fever being less common. Prodromal pain lasts three to four days but it can extend to a week. A maculopapular rash develops into clusters of vesicles. Characteristic rash appears as vesicles on an erythematous base. New vesicles continue to appear over three to four days. The rash is usually accompanied by the same pain during prodromal, but this acute phase pain can worsen, improve, or appear for the first time. VZV can cause viremia. In immunocompromised persons, extensive viremia can lead to disseminated form of zoster.
xPostherpetic neuralgia (PHN) is the most common complication of herpes zoster. It is diagnosed as pain persisting for an extended period after onset of zoster rash. Other complications include ophthalmic involvement, bacterial superinfections of the lesions, cranial and peripheral nerve palsies, meningoencephalitis, pneumonitis, hepatitis, and acute retinal necrosis.
Zostavax®, a live attenuated vaccine, was licenced for normal individuals and contraindicated in those with no prior history of varicella and immunocompromised populations. It is now no longer for use in many countries including Malaysia. Recombinant zoster vaccine has replaced zoster live attenuated vaccine.
- The recombinant zoster vaccine (RZV, Shingrix®) is a 2-dose subunit vaccine that will provide protection for normal persons and immunocompromised patients. It is suitable for immunocompromised populations because the risk of virus replication does not occur. It consists of the major envelope glycoprotein E (gE) antigen component and AS01B adjuvant suspension component to help enhance the immune response. Glycoprotein E was selected as candidate vaccine antigen because it is essential for viral replication, cell to cell spread, target for VZV-specific immune response and the most abundant on infected cells. AS01B adjuvant system promotes CD4 T cell and humoral immune response. It is produced by GSK Biologicals. This vaccine has been marketed in many countries (including Singapore) since 2017. In July 2021, The Food and Drug Administration US expanded the use of RZV to include immunodeficient or immunosuppressed adults aged > 18 years. It is going to be launched in Malaysia very soon.
- The recombinant zoster vaccine (RZV, Shingrix®) is the only vaccine available for zoster worldwide.
Vaccines Available in Malaysia
Currently no vaccines are available as ZOSTAVAX is no longer marketed in Malaysia. However, the recombinant vaccine is expected to be available in Malaysia in the near future. It is currently available in many other countries, including Singapore.
Mode of Administration
RZV, a 2-dose subunit vaccine, is administered intramuscularly, the second dose administered 2-6 months after the first dose.
For individuals who are immunodeficient would benefit from a shorter vaccination schedule; the second dose may be administered 1 to 2 months after the first dose.
Co-administration with Other Vaccines
In immunocompetent persons, RZV can be administered concomitantly, at different anatomical sites, with influenza vaccine, Pneumococcal Polysaccharide Vaccine PPV23 and Pneumococcal Conjugate Vaccine PCV13.
Immunogenicity of 2 doses of RZV was unaffected by co-administration of seasonal influenza vaccine. Likewise, immunogenicity of influenza vaccine was not substantially affected by co-administration of RZV.
Humoral response to co-administration of RZV and Pneumococcal Polysaccharide Vaccine PPSV23 was non inferior to sequential administration.
Contraindications and Adverse Effects
- Recombinant Zoster Vaccine should not be given to:
>> Persons who have history of severe allergic reaction to any component of the vaccine or after previous dose of recombinant zoster vaccine.
>> Persons experiencing acute episode of herpes zoster. Recombinant zoster vaccine is not a treatment for herpes zoster or postherpetic neuralgia (PHN).
- Adverse effects include mild to moderate pain at injection site, fatigue, myalgia and headache which resolve within 3 days.
Target Groups in Malaysia
Recombinant Zoster vaccine is recommended for persons who are 50 years and above, provided there are no contraindications. Recombinant Zoster Vaccine may be given regardless of whether or not they have had prior history of varicella or herpes zoster (shingles) infection.
Recombinant Zoster vaccine is recommended for immunosuppressed patients 18 years and above, provided there are no contraindications.
Implications for Healthcare Workers (HCWs)
Healthcare workers should receive the vaccination as they are at higher risk of exposure to varicella-zoster virus, and they may also be the source of varicella infection (chickenpox) to their patients.
Evidence for Effectiveness
Evidence for immunocompetent persons
Efficacy of recombinant zoster vaccine (RZV) for prevention of herpes zoster in 3- year studies, was 97.2% in persons aged > 50 years and 89.9% in participants aged >70 years. In 2017, ACIP recommended it for the use of immunocompetent adults aged 50 years and above.
Humoral and cellular immune responses persisted for 10 years in older adults after initial 2-dose RZV. Additional dosing after 10 years elicit strong anamnestic immune response.
Humoral immune response to RZV post 2-dose was non inferior in adults >65 years who were previously vaccinated with live attenuated zoster vaccine Zostavax(ZVL) > 5 years ago compared to ZVL- naïve adults. RZV was well tolerated in both study groups and no safety concerns were identified up to one month post dose 2.
- Efficacy of recombinant zoster vaccine in prevention of zoster in immunocompromised autologous haematopoietic stem cell transplantation (HSCT) recipients was 68.2 %.
- Immunogenicity and safety studies on patients with haematological malignancies proved that humoral and cellular immune responses persisted above the baseline 13 months after vaccination. Post hoc analysis vaccine efficacy of 87.2% against herpes zoster in population of immunocompromised adults 18 years and older. The safety profile was acceptable in adults with haematological malignancies.
- Recombinant zoster vaccines were immunogenic in patients with solid tumours receiving immunosuppressive therapy regime. Immunogenicity persisted 12 months after vaccination regardless of timing of first vaccination in relation to start of chemotherapy.
- Recombinant zoster vaccine was immunogenic in renal transplant patient > 18 years age under chronic daily suppression and the immunogenicity persisted through one year after vaccination.
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