Guidelines for Adult Immunisation

Available Vaccines

Zoster

Updated in November 2023

Introduction

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. 

Postherpetic 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.

 

Vaccines

 
  • 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. 

Evidence for immunocompromised patients 
 
  • 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.

References

  1. Levin MJ. Zoster vaccine in Stanley Plotkin, Walter Orenstein ,Paul Offit and Kathryn Edwards. Plotkin’s Vaccines. Seventh Edition. Saunders Elsevier. 2018
  2. Lal H, Cunningham AL, Godeaux O et al. Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults. N Engl J Med 2015;372:2087‒96.
  3. Cunningham AL, Lal H,Kovac M et al. Efficacy of the Herpes Zoster Subunit Vaccine in Adults 70 Years of Age or Older. N Engl J Med 2016;75:1019‒32.
  4. CDC. Use of recombinant zoster Vaccine in Immunocompromise. MMWR Jan 21,2022/71(3);80-84
  5. A. Hastie. Immunogenicity of Adjuvanted Recombinant Zoster Vaccine: Persistence and Anamnestic Response to Additional Doses Administered 10 years After Primary Vaccination. JID 2021:224:2025-2034
  6.  Marechal et al. Immunogenicity and safety of the adjuvanted recombinant zoster vaccine co-administered with the 23-valent pneumococcal polysaccharide vaccine in adults 50 years of age: A randomized trial .Vaccine 2018 ;:4278-428
  7. Schwarz et al Immunogenicity and Safety of an Adjuvanted Herpes Zoster Subunit Vaccine Coadministered With Seasonal Influenza Vaccine in Adults Aged 50 Years or Older . JID2017 :216:1352-1361
  8. Marta Lez Fauqued et al. Safety Profile of the Adjuvanted Recombinant Zoster Vaccine in Immunocompromised Populations: An Overview of Six Trials. Drug Safety 2021;44:811–823
  9. Adriana Bastidas, Javier de la Serna, Mohamed El Idrissi .Effect of Recombinant Zoster Vaccine on Incidence of Herpes Zoster After Autologous Stem Cell Transplantation A Randomized Clinical Trial JAMA. 2019;322(2):123-133
  10. Alemnew F Dagnew, Osman Ilhan, Won-Sik Lee et al.  Immunogenicity and safety of the adjuvanted recombinant zoster vaccine in adults with haematological malignancies: a phase 3, randomised, clinical trial and post-hoc efficacy analysis Lancet Infect Dis  Aug 6, 2019 :1-13
  11. Peter Vink, Josep Maria Ramon Torrell,Ana Sanchez Fructuoso .Immunogenicity and Safety of the Adjuvanted Recombinant Zoster Vaccine in Chronically Immunosuppressed Adults Following Renal Transplant: A Phase 3, Randomized Clinical Trial. Clin Inf Ds2020:70 (15 January) :181 -190
  12. Peter Vink, Ignacio Delgado Mingorance, Constanza Maximiano Alonso, Immunogenicity and Safety of the Adjuvanted Recombinant Zoster Vaccine in Patients With Solid Tumors, Vaccinated Before or During Chemotherapy: A Randomized Trial . Cancer April 15, 2019 :1301-131
  13. Grupping K, Campora L, Douha M, Heineman TC, Klein NP, Lal H, Peterson J, Vastiau I, Oostvogels. Immunogenicity and Safety of the HZ/su Adjuvanted Herpes Zoster Subunit Vaccine in Adults Previously Vaccinated With a Live Attenuated Herpes Zoster Vaccine 2017. J  Infect Dis. 2017 Dec 12;216(11):1343-1351.