Evaluation of Recombinant Herpes Zoster Vaccine for Primary Immunization of Varicella-seronegative Transplant Recipients

Transplantation. 2021 Oct 1;105(10):2316-2323. doi: 10.1097/TP.0000000000003621.

Abstract

Background: Immunization of varicella-zoster virus (VZV)-seronegative solid organ transplant (SOT) patients using the live-attenuated varicella vaccine is generally contraindicated, leaving no widely applicable immunization option. The recombinant subunit herpes zoster vaccine (RZV) is indicated for VZV-seropositive persons to prevent shingles but could potentially also protect VZV-seronegative persons against varicella. We performed a safety and immunogenicity evaluation of RZV in VZV-seronegative SOT recipients as an option for protection.

Methods: VZV-seronegative adult SOT patients with no history of varicella/shingles vaccine or disease were given 2 doses of RZV vaccine 2-6 mo apart. Blood was drawn prevaccination (V1), before the second dose (V2), and 4 wk after the second dose (V3). Humoral immunity (anti-glycoprotein E) and cell-mediated immunity were evaluated, with polyfunctional cells defined as cells producing ≥2 cytokines.

Results: Among 31 eligible VZV-seronegative SOT patients screened, 23 were enrolled. Median age was 38 y and median time since transplant procedure was 3.8 y. The most frequent transplant types were liver (35%) and lung (30%). Median anti-glycoprotein E levels significantly increased from V1 to V3 (P = 0.001) and V2 to V3 (P < 0.001), even though only 55% had a positive seroresponse. Median polyfunctional CD4 T-cell counts increased from V1 to V2 (54/106 versus 104/106 cells; P = 0.041) and from V2 to V3 (380/106; P = 0.002). Most adverse events were mild with no rejection episodes.

Conclusions: RZV was safe and elicited significant humoral and cellular responses in VZV-seronegative SOT patients and has the potential to be considered as a preventive strategy against primary varicella.

Trial registration: ClinicalTrials.gov NCT03685682.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Viral / blood
  • Biomarkers / blood
  • Female
  • Herpes Zoster Vaccine / administration & dosage*
  • Herpes Zoster Vaccine / adverse effects
  • Herpesvirus 3, Human / immunology*
  • Herpesvirus 3, Human / pathogenicity
  • Humans
  • Immunity, Cellular / drug effects
  • Immunity, Humoral / drug effects
  • Immunization
  • Immunogenicity, Vaccine*
  • Male
  • Middle Aged
  • Organ Transplantation* / adverse effects
  • Proof of Concept Study
  • Prospective Studies
  • Time Factors
  • Treatment Outcome
  • Vaccines, Synthetic / administration & dosage
  • Varicella Zoster Virus Infection / immunology
  • Varicella Zoster Virus Infection / prevention & control*
  • Varicella Zoster Virus Infection / virology
  • Viral Envelope Proteins / immunology

Substances

  • Antibodies, Viral
  • Biomarkers
  • Herpes Zoster Vaccine
  • Vaccines, Synthetic
  • Viral Envelope Proteins
  • glycoprotein E, varicella-zoster virus

Associated data

  • ClinicalTrials.gov/NCT03685682