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Blood, 1 August 2004, Vol. 104, No. 3, pp. 847-856. Prepublished online as a Blood First Edition Paper on April 15, 2004; DOI 10.1182/blood-2003-10-3469. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-10-3469v1 104/3/847    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wang, Z. Articles by Diamond, D. J. Search for Related Content PubMed PubMed Citation Articles by Wang, Z. Articles by Diamond, D. J. Related Collections Immunobiology Transplantation Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Attenuated poxviruses generate clinically relevant frequencies of CMV-specific T cells Zhongde Wang, Corinna La Rosa, Shahram Mekhoubad, Simon F. Lacey, Maria C. Villacres, Susan Markel, Jeff Longmate, Joshua D. I. Ellenhorn, Robert F. Siliciano, Christopher Buck, William J. Britt, and Don J. Diamond From the Laboratory of Vaccine Research, Beckman Research Institute of the City of Hope, Division of Information Sciences, and Division of General and Oncologic Surgery, City of Hope Comprehensive Cancer Center, Duarte, CA; the Division of Medicine, Johns Hopkins University Medical School, Baltimore, MD; and the Department of Pediatrics, University of Alabama, Birmingham, AL. Immunotherapeutic approaches to limit cytomegalovirus (CMV) morbidity and mortality after hematopoietic stem cell transplants (HSCTs) are currently under investigation as alternatives to antiviral drugs. In this context, we have inserted full-length and ubiquitin-modified CMV phosphoprotein 65 (pp65), phosphoprotein 150 (pp150), and immediate early protein 1 (IE1) immunodominant antigens into the virulent Western Reserve strain of vaccinia virus (VV) and the highly attenuated strain, modified vaccinia Ankara (MVA). Recombinant (r) VV or rMVA stimulated vigorous expansion of CMV-specific CD8+ T cells in CMV-positive donor peripheral blood mononuclear cells (PBMCs), which showed minimal alloreactivity and high levels of HLA tetramer binding, cytokine production, and cytotoxicity. Ubiquitinated antigens had a profound effect when expressed in VV. Single antigen rMVA expressing pp65 or IE1, either ubiquitin-modified or native, stimulated both cytotoxic T lymphocyte (CTL) populations to be expanded up to 500-fold in a 60-mL blood draw from the same donor. This result demonstrates the clinical feasibility of simultaneously amplifying multiple CMV-CTL populations. Transgenic HLA A2.1 (HHD II) mice, immunized with the same rMVA as used with human PBMCs, produced a robust cytotoxic response to both CMV pp65 and IE1. The specificity of the vigorous immunologic response to rMVA, both in vitro and in vivo, makes them candidates for clinical evaluation in the context of adoptive immunotherapy for hematopoietic stem cell transplant (HSCT) recipients or donor vaccination. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: N. Khan, D. Best, R. Bruton, L. Nayak, A. B. Rickinson, and P. A. H. Moss T Cell Recognition Patterns of Immunodominant Cytomegalovirus Antigens in Primary and Persistent Infection J. Immunol., April 1, 2007; 178(7): 4455 - 4465. [Abstract] [Full Text] [PDF] Y. Yue, A. Kaur, S. S. Zhou, and P. A. Barry Characterization and immunological analysis of the rhesus cytomegalovirus homologue (Rh112) of the human cytomegalovirus UL83 lower matrix phosphoprotein (pp65). J. Gen. Virol., April 1, 2006; 87(Pt 4): 777 - 787. [Abstract] [Full Text] [PDF] S. Delmas, L. Martin, M. Baron, J. A. Nelson, D. N. Streblow, and J.-L. Davignon Optimization of CD4+ T Lymphocyte Response to Human Cytomegalovirus Nuclear IE1 Protein through Modifications of Both Size and Cellular Localization J. Immunol., November 15, 2005; 175(10): 6812 - 6819. [Abstract] [Full Text] [PDF]

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