← Back to December 2017


New Shingles Vaccine


links image

Georgina Waldman, PharmD
University of California San Diego Health
San Diego, CA, USA
Gwaldman@ucsd.edu



Vaccination is a core component of preventing infection. However, immunosuppressed patients have a reduced response to vaccination which is multifactorial, influenced by type of immunosuppression, time from transplantation and type of graft. Due to this blunted response, we optimize all vaccinations prior to transplant, particularly post-transplant contraindicated live vaccines. However, not all patients are able to be fully immunized prior to transplant or may not have developed full immunity, leading to risk of infection post-transplant. This has been an issue especially with herpes zoster (HZ), a reactivation of varicella-zoster virus (VZV) in the posterior dorsal root ganglion.

Prior to the approval of the zoster vaccine live (Zostavax®┬«) in 2006, reported incidence of HZ infections was 8-12% for lung and 20-25% for heart transplants, though there was wide variance likely due to differences in protocols across centers [1,2].

Development of HZ post-transplant is associated with higher healthcare costs, VZV hyperimmune gamma-glubulin is not currently widely available and may be cost prohibitive [3]. Therefore, when the live zoster vaccine was approved, its use in the pre-transplant phase was highly recommended. Currently, the 2013 IDSA guidelines recommend zoster vaccine live at least 4 weeks prior to transplantation in candidates aged ≥60 years and varicella-positive candidates (aged 50-59 years) but not in immunocompromised patients [4].

Recently, a new zoster vaccine was approved for use in immunocompetent individuals -the inactivated HZ subunit vaccine (HZ/su), Shingrix┬«. In October 2017, Shingrix® was approved in the United States and Canada while regulatory filings in the European Union, Australia and Japan are underway [4]. It is a recombinant, adjuvanted combination subunit vaccine that mixes a lyophilized surface glycoprotein E antigen with a AS01b adjuvant [6]. The ZOE-50 trial first paved the way to approval and found an 97.2% efficacy against HZ in patients over the age of 50, a marked improvement over the zoster vaccine live reported efficacy of 51% [7,8]. The most common side effects of HZ/su are injection site pain, redness and swelling. Muscle pain, headache, fever, shivering and GI upset have also been reported with most lasting less than 3 days.6 Two doses of the vaccine are required to gain immunity for immunocompetent patients at 0 and 2 - 6 months.6 However, one study in adult heamtopietic stem cell transplant (HSCT) recipients studied HZ/su in three doses at 0, 1 and 3 months [9]. This vaccination schedule gave acquired humor and cellular immunity equivalent to immunocompetent individuals post two doses of vaccine, even when initiated two months post-transplant.

Per GSK, a phase III, observer-blinded, placebo controlled study to evaluate efficacy, safety and immunogenicity of HZ/su vaccine administered as a 2-dose schedule, in autologous HSCT recipients 18 years of age and older has been completed (ClinicalTrials.gov identifier: NCT01610414) [10]. Study results will be available in December 2017.

Shingrix® has been found to be effective in patients that have previously received the live vaccine, Zosatvax® as well [11,12]. Another study assessed the impact of co-administration of HZ/su and inactivated influenza at the same time and found no significant difference efficacy with co-administration [13].

Questions of transplant patients and their household contacts often arise. Current recommendations from the IDSA state that healthy immunocompetent individuals who live in a household with immunocompromised patients should receive their vaccinations, including live vaccines, based on the CDC annual schedule recommendations [4]. However, our patients should avoid contact with persons who develop skin lesions following the varicella live vaccine or the zoster vaccine live until the lesions clear, though risk of transmission is low.

After years of difficulty in management of this painful infection post-transplant it appears that we will now have a safe and effective preventative vaccine for our transplant patients. Further studies are always needed to truly assess the safety in our unique population, and it is uncertain the financial burden on our patient's will be but at the moment, the future is looking bright. ■

Disclosure Statement: The author has no conflicts of interest to disclose.


References:

  1. Gnann JW. Other herpesviruses: Herpes simplex virus, varicella-zoster virus, human herpes types 6, 7, and 8. In: Transplant Infec-tions, 1stedn. Philadelphia: Lippincott-Raven, 1998: 265-86.
  2. Gourishankar S, McDermid JC, Jhangri GS, Preiksaitis JK. Herpes zoster infection following solid organ transplantation: incidence, risk factors and outcomes in the current immunosuppressive era. Am J Transplant. 2004;4(1):108-15.
  3. Palmer L, White RR, Johnson BH, et al. Herpes zoster-attributable resource utilization and cost burden in patients with solid organ transplant. Transplantation. 2014;97(11):1178-84.
  4. Rubin LG, Levin MJ, Ljungman P, et al. 2013 IDSA Clinical Practice Guideline for Vaccination of the Immunocompromised Host. Clin Infect Dis. 2014;58(3):e44-e100.
  5. Shingrix approved in the US for prevention of shingles in adults aged 50 and over. GSK, 2017. (https://www.gsk.com/en-gb/media/press-releases/shingrix-approved-in-the-us-for-prevention-of-shingles-in-adults-aged-50-and-over/). Accessed November 15, 2017.
  6. Shingrix [package insert]. Triangle Park, NC: GlaxoSmithKline Biologicals; 2017.
  7. Lal H, Cunningham AL, Godeaux O, et al. Efficacy of an adjuvated herpes zoster subunit vaccine in older adults. N Engl J Med. 2015;372:2087-96.
  8. 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
  9. Stadmauer EA, Sullivan KM, Marty FM, et al. A phase 1/2 study of an adjuvanted varicella-zoster virus subunit vaccine in autologous hematopoietic cell transplant recipients. Blood 2014;124(19):2921-2929.
  10. Clinicaltrials.gov. (2017). Study to Evaluate Efficacy, Safety, and Immunogenicity of GlaxoSmithKline (GSK) Biologicals' Herpes Zoster Vaccine GSK1437173A - ClinicalTrials.gov. [online] Available at: https://clinicaltrials.gov/ct2/show/NCT01610414?term=NCT01610414&rank=1 [Accessed 19 Nov. 2017].
  11. Grupping K, Campora L, Douha M, et al. Immunogenicity and safety of the HZ/su adjuvanted herpes zoster subunit vaccine in adults previously vaccinated with a live-attenuated herpes zoster vaccine. J Infect Dis. 2017; doi: 10.1093/infdis/jix482. [Epub ahead of print]
  12. Colindres R. Immunogenicity and safety of Shingrix in adults previously vaccinated with a live-attentunated herpes zoster vaccine (Zoster-048 Study). Presented at ACIP, June 2017.
  13. Schwarz TF, Aggarwal N, Moeckesch B, et al. Immunogenicity and safety of an adjuvanted herpes zoster subunit vaccine co-administered with seasonal influenza vaccine in adults aged 50 years and older. J Infect Dis. 2017; doi: 10.1093/infdis/jix481. [Epub ahead of print]



Share via:

links image    links image    links image    links image