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Use of Subunit Herpes Zoster Vaccine in VZV-Seronegative Transplant Recipients to Prevent Primary Varicella

A. G. L'Huillier1, V. H. Ferreira2, C. Hirzel3, M. Ierullo2, T. Ku2, N. Selzner2, J. Schiff2, J. Tikkanen2, C. Miao4, D. S. Schmid4, A. Humar2, D. Kumar2

1HUG, Geneva, Switzerland, 2UHN, Toronto, ON, Canada, 3Inselspital, Bern, Switzerland, 4CDC, Atlanta, GA

Meeting: 2020 American Transplant Congress

Abstract number: 376

Keywords: FACS analysis, Immunogenicity, T cells, Vaccination

Session Information

Date: Saturday, May 30, 2020

Session Name: CMV and other Herpes Viruses

Session Time: 3:15pm-4:45pm

 Presentation Time: 3:15pm-3:27pm

Location: Virtual

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*Purpose: Varicella-zoster virus (VZV) primary infection can be prevented by using the live varicella vaccine. However, this is contraindicated after organ transplant. We investigated the non-live recombinant subunit herpes zoster vaccine (RZV) as a novel strategy to prevent primary varicella in VZV-seronegative transplant recipients.

*Methods: Adult SOT patients who were VZV-seronegative and had no history of varicella/shingles vaccine or disease were enrolled and given two doses of RZV vaccine 2-6 months apart. Blood was drawn pre-vaccination (V1), just prior to the second dose (V2) and 4 weeks after second dose (V3).Humoral immunity was evaluated by anti-gE antibodies and a positive seroresponse was defined as a baseline optical density value higher than two standard deviations above the mean. Cell-mediated immunity assays were performed after stimulating PBMCs with a VZV peptide pool. Polyfunctional cells were defined as cells producing at least two cytokines among IFNγ, TNFα, IL2 and CD40L.

*Results: Among 31 eligible VZV seronegative SOT patients screened, 23 were enrolled.Median age was 38 yrs (range 18-67) and median time since SOT was 3.8 yrs (range 0.2-22.6). Transplant types were liver (35%), lung (30%), kidney (17%) and combined (17%). Most patients (78%) were on triple immunosuppression. Median anti-gE levels significantly increased from V1 to V3 (p=0.001) and V2 to V3 (p<0.001). Three patients had baseline positive anti-gE serology. Among the remaining 20 patients, 11 (55%) had a positive seroresponse to the vaccine. There was a trend towards lower median anti-gE antibodies at V3 among thoracic transplant recipients compared to other organs (p=0.076). Median anti-gE avidity increased from V1 to V3 (0 vs. 12%;p=0.002). Polyfunctional CD4 T-cells significantly increased from V1 to V2 (median 54/106 vs 104/106cells; p=0.041), and from V2 to V3 (380/106; p=0.002). Lung transplant recipients had lower median polyfunctional CD4 T-cells at V3 (99/106) than other organ transplant recipients (540/106; p=0.015). Anti-gE titers and polyfunctional CD4 T-cells at V3 were positively correlated (correlation coefficient (CC) 0.515; p=0.014). The use of prednisone and mycophenolate was associated with significantly lower anti-gE responses (p=0.046 and 0.004 respectively). Increasing doses of prednisone or mycophenolate were associated with lower polyfunctional CD4 T-cell responses at V3 (CC -0.361; p=0.09 and CC -0.593; p=0.009 respectively). There was no significant increase in polyfunctional CD8 T-cells after the vaccine.

*Conclusions: RZV was safe and elicited significant humoral and cellular responses in VZV-seronegative SOT patients. We provide the first unique data that RZV may be considered as a preventive strategy against primary varicella in transplant recipients who are VZV-naïve.

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To cite this abstract in AMA style:

L'Huillier AG, Ferreira VH, Hirzel C, Ierullo M, Ku T, Selzner N, Schiff J, Tikkanen J, Miao C, Schmid DS, Humar A, Kumar D. Use of Subunit Herpes Zoster Vaccine in VZV-Seronegative Transplant Recipients to Prevent Primary Varicella [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/use-of-subunit-herpes-zoster-vaccine-in-vzv-seronegative-transplant-recipients-to-prevent-primary-varicella/. Accessed March 1, 2021.

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