TY - JOUR AU - Patrick Kleemann, AU - Eva Distler, AU - Eva M. Wagner, AU - Simone Thomas, AU - Sebastian Klobuch, AU - Steffi Aue, AU - Elke Schnürer, AU - Hansjörg Schild, AU - Matthias Theobald, AU - Bodo Plachter, AU - Stefan Tenzer, AU - Ralf G. Meyer, AU - Wolfgang Herr, PY - 2012/06/04 Y2 - 2024/03/29 TI - Varicella-zoster virus glycoproteins B and E are major targets of CD4+ and CD8+ T cells reconstituting during zoster after allogeneic transplantation JF - Haematologica JA - haematol VL - 97 IS - 6 SE - Articles DO - 10.3324/haematol.2011.052597 UR - https://haematologica.org/article/view/6326 SP - 874-882 AB - Background After allogeneic hematopoietic stem-cell transplantation patients are at increased risk for herpes zoster as long as varicella-zoster virus specific T-cell reconstitution is impaired. This study aimed to identify immunodominant varicella-zoster virus antigens that drive recovery of virus-specific T cells after transplantation.Design and Methods Antigens were purified from a varicella-zoster virus infected cell lysate by high-performance liquid chromatography and were identified by quantitative mass spectrometric analysis. To approximate in vivo immunogenicity for memory T cells, antigen preparations were consistently screened with ex vivo PBMC of varicella-zoster virus immune healthy individuals in sensitive interferon-γ ELISpot assays. Candidate virus antigens identified by the approach were genetically expressed in PBMC using electroporation of in vitro transcribed RNA encoding full-length proteins and were then analyzed for recognition by CD4+ and CD8+ memory T cells.Results Varicella-zoster virus encoded glycoproteins B and E, and immediate early protein 62 were identified in immunoreactive lysate material. Predominant CD4+ T-cell reactivity to these proteins was observed in healthy virus carriers. Furthermore, longitudinal screening in allogeneic stem-cell transplantation patients showed strong expansions of memory T cells recognizing glycoproteins B and E after onset of herpes zoster, while immediate early protein 62 reactivity remained moderate. Reactivity to viral glycoproteins boosted by acute zoster was mediated by both CD4+ and CD8+ T cells.Conclusions Our data demonstrate that glycoproteins B and E are major targets of varicella-zoster virus specific CD4+ and CD8+ T-cell reconstitution occurring during herpes zoster after allogeneic stem-cell transplantation. Varicella-zoster virus glycoproteins B and E might form the basis for novel non-hazardous zoster subunit vaccines suitable for immunocompromised transplant patients. ER -