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Prepublished online as a Blood First Edition Paper on July 12, 2002; DOI 10.1182/blood-2002-03-0926. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-03-0926v1 100/10/3681    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 La Rosa, C. Articles by Diamond, D. J. Search for Related Content PubMed PubMed Citation Articles by La Rosa, C. Articles by Diamond, D. J. Related Collections Immunobiology Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 November 2002, Vol. 100, No. 10, pp. 3681-3689 IMMUNOBIOLOGY Preclinical development of an adjuvant-free peptide vaccine with activity against CMV pp65 in HLA transgenic mice Corinna La Rosa, Zhongde Wang, John C. Brewer, Simon F. Lacey, Maria C. Villacres, Rahul Sharan, Radhika Krishnan, Matthew Crooks, Susan Markel, Rebecca Maas, and Don J. Diamond From the Laboratory of Vaccine Research, Division of Virology, Beckman Research Institute of the City of Hope, Duarte, CA 91010. Epitope vaccines have shown promise for inducing cellular immune responses in animal models of infectious disease. In cases where cellular immunity was augmented, peptide vaccines composed of covalently linked minimal cytotoxic T-lymphocyte (CTL) and T-helper (TH) epitopes generally showed the most efficacy. To address a clinical vaccine strategy for cytomegalovirus (CMV) in the context of HCT (hematopoietic cell transplantation), we observed that linking the synthetically derived pan-DR epitope peptide (PADRE) or one of several tetanus TH epitopes to the immunodominant human leukocyte antigen (HLA) A*0201-restricted CTL epitope from CMV-pp65 to create a fusion peptide caused robust cytotoxic cellular immune responses in HLA A*0201/Kb transgenic mice. Significantly, the fusion peptides are immunogenic when administered in saline solution by either subcutaneous or intranasal routes. CpG-containing single-stranded DNA (ss-oligodeoxynucleotide [ODN]) added to the fusion peptides dramatically up-regulated immune recognition by either route. Notably, target cells that either expressed full-length pp65 protein from vaccinia viruses or were sensitized with the CTL epitope encoded in the vaccine were recognized by splenic effectors from immunized animals. Visualization of murine peptide-specific CTL by flow cytometry was accomplished using an HLA A*0201 tetramer complexed with the pp65495-503 CTL epitope. TH-CTL epitope fusion peptides in combination with CpG ss-ODN represent a new strategy for parenteral or mucosal delivery of vaccines in a safe and effective manner that has applicability for control or prophylaxis of infectious disease, especially in situations such as vaccination of donors or recipients of HCT, where highly inflammatory adjuvants are not desired. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: 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] L. Krymskaya, M. C. Sharma, J. Martinez, W. Haq, E. C. Huang, A. P. Limaye, D. J. Diamond, and S. F. Lacey Cross-Reactivity of T Lymphocytes Recognizing a Human Cytotoxic T-Lymphocyte Epitope within BK and JC Virus VP1 Polypeptides J. Virol., September 1, 2005; 79(17): 11170 - 11178. [Abstract] [Full Text] [PDF] M. G. Agadjanyan, A. Ghochikyan, I. Petrushina, V. Vasilevko, N. Movsesyan, M. Mkrtichyan, T. Saing, and D. H. Cribbs Prototype Alzheimer's Disease Vaccine Using the Immunodominant B Cell Epitope from {beta}-Amyloid and Promiscuous T Cell Epitope Pan HLA DR-Binding Peptide J. Immunol., February 1, 2005; 174(3): 1580 - 1586. [Abstract] [Full Text] [PDF] C. S. Morello, M. Ye, S. Hung, L. A. Kelley, and D. H. Spector Systemic Priming-Boosting Immunization with a Trivalent Plasmid DNA and Inactivated Murine Cytomegalovirus (MCMV) Vaccine Provides Long-Term Protection against Viral Replication following Systemic or Mucosal MCMV Challenge J. Virol., January 1, 2005; 79(1): 159 - 175. [Abstract] [Full Text] [PDF] Z. Wang, C. La Rosa, S. Mekhoubad, S. F. Lacey, M. C. Villacres, S. Markel, J. Longmate, J. D. I. Ellenhorn, R. F. Siliciano, C. Buck, et al. Attenuated poxviruses generate clinically relevant frequencies of CMV-specific T cells Blood, August 1, 2004; 104(3): 847 - 856. [Abstract] [Full Text] [PDF] B. Wang, H. Chen, X. Jiang, M. Zhang, T. Wan, N. Li, X. Zhou, Y. Wu, F. Yang, Y. Yu, et al. Identification of an HLA-A*0201-restricted CD8+ T-cell epitope SSp-1 of SARS-CoV spike protein Blood, July 1, 2004; 104(1): 200 - 206. [Abstract] [Full Text] [PDF] Z. Wang, C. La Rosa, R. Maas, H. Ly, J. Brewer, S. Mekhoubad, P. Daftarian, J. Longmate, W. J. Britt, and D. J. Diamond Recombinant Modified Vaccinia Virus Ankara Expressing a Soluble Form of Glycoprotein B Causes Durable Immunity and Neutralizing Antibodies against Multiple Strains of Human Cytomegalovirus J. Virol., April 15, 2004; 78(8): 3965 - 3976. [Abstract] [Full Text] [PDF] P. Daftarian, S. Ali, R. Sharan, S. F. Lacey, C. La Rosa, J. Longmate, C. Buck, R. F. Siliciano, and D. J. Diamond Immunization with Th-CTL Fusion Peptide and Cytosine-Phosphate-Guanine DNA in Transgenic HLA-A2 Mice Induces Recognition of HIV-Infected T Cells and Clears Vaccinia Virus Challenge J. Immunol., October 15, 2003; 171(8): 4028 - 4039. [Abstract] [Full Text] [PDF]

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