@article{Patrick Kleemann_Eva Distler_Eva M. Wagner_Simone Thomas_Sebastian Klobuch_Steffi Aue_Elke Schnürer_Hansjörg Schild_Matthias Theobald_Bodo Plachter_Stefan Tenzer_Ralf G. Meyer_Wolfgang Herr_2012, place={Pavia, Italy}, title={Varicella-zoster virus glycoproteins B and E are major targets of CD4+ and CD8+ T cells reconstituting during zoster after allogeneic transplantation}, volume={97}, url={https://haematologica.org/article/view/6326}, DOI={10.3324/haematol.2011.052597}, abstractNote={<strong>Background</strong> 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.<strong>Design and Methods</strong> 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 <em>in vivo</em> immunogenicity for memory T cells, antigen preparations were consistently screened with <em>ex vivo</em> 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 <em>in vitro</em> transcribed RNA encoding full-length proteins and were then analyzed for recognition by CD4<sup>+</sup> and CD8<sup>+</sup> memory T cells.<strong>Results</strong> Varicella-zoster virus encoded glycoproteins B and E, and immediate early protein 62 were identified in immunoreactive lysate material. Predominant CD4<sup>+</sup> 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<sup>+</sup> and CD8<sup>+</sup> T cells.<strong>Conclusions</strong> Our data demonstrate that glycoproteins B and E are major targets of varicella-zoster virus specific CD4<sup>+</sup> and CD8<sup>+</sup&gt; 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.}, number={6}, journal={Haematologica}, author={Patrick Kleemann and Eva Distler and Eva M. Wagner and Simone Thomas and Sebastian Klobuch and Steffi Aue and Elke Schnürer and Hansjörg Schild and Matthias Theobald and Bodo Plachter and Stefan Tenzer and Ralf G. Meyer and Wolfgang Herr}, year={2012}, month={Jun.}, pages={874-882} }