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,
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*
Center for Cell and Gene Therapy and Departments of
Molecular and Human Genetics and
Immunology, Baylor College of Medicine, Houston, TX 77030; and
Department of Bioengineering, Rice University, Houston, TX 77030
HIV-1 is a fundamentally difficult target for vaccines due to its
high mutation rate and its repertoire of immunoevasive strategies. To
address these difficulties, a multivalent, proteasome-targeted, live
genetic vaccine was recently developed against HIV-1 using the
expression library immunization approach. In this HIV-1 vaccine all
open reading frames of HIV-1 are expressed from 32 plasmids as Ag
fragments fused to the ubiquitin protein to increase Ag targeting to
the proteasome to enhance CTL responses. In this work we demonstrate
the ability of the HIV-1 library vaccine to simultaneously provoke
robust HLA-A*0201-restricted T cell responses against all 32 HIV-1
library vaccine Ags after single immunization by gene gun. These CD8 T
cell responses included HLA-A*0201-restricted CTL activity, CD8/IFN-
T cell responses, and HLA tetramer binding against defined
immunodominant epitopes in gag, pol, env, and nef as well as potent
CD8/IFN- responses against undefined HLA-A*0201-restricted epitopes
in all remaining Ags of the library. CD8 responses mediated by single
gag, pol, env, and nef plasmids from the vaccine demonstrated little
reduction in specific T cell responses when these plasmids were diluted
into the context of the full 32-plasmid library, suggesting that Ag
dominance or immune interference is not an overt problem to limit the
efficacy of this complex vaccine. Therefore, this work demonstrates the
ability of the HIV-1 library vaccine to generate robust multivalent
genome-wide T cell responses as one approach to control the highly
mutable and immunoevasive HIV-1 virus.
This article has been cited by other articles:
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  A. M. Talaat and K. Stemke-Hale Expression Library Immunization: a Road Map for Discovery of Vaccines against Infectious Diseases Infect. Immun., November 1, 2005; 73(11): 7089 - 7098. [Full Text] [PDF]
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 A. Boesen, K. Sundar, and R. Coico Lassa Fever Virus Peptides Predicted by Computational Analysis Induce Epitope-Specific Cytotoxic-T-Lymphocyte Responses in HLA-A2.1 Transgenic Mice Clin. Vaccine Immunol., October 1, 2005; 12(10): 1223 - 1230. [Abstract] [Full Text] [PDF]
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 F. K. Stevenson, C. H. Ottensmeier, P. Johnson, D. Zhu, S. L. Buchan, K. J. McCann, J. S. Roddick, A. T. King, F. McNicholl, N. Savelyeva, et al. DNA vaccines to attack cancer PNAS, October 5, 2004; 101(suppl_2): 14646 - 14652. [Abstract] [Full Text] [PDF]
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 R. A. K. Singh and M. A. Barry Repertoire and Immunofocusing of CD8 T Cell Responses Generated by HIV-1 gag-pol and Expression Library Immunization Vaccines J. Immunol., October 1, 2004; 173(7): 4387 - 4393. [Abstract] [Full Text] [PDF]
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J. Rice, S. Buchan, H. Dewchand, E. Simpson, and F. K. Stevenson DNA Fusion Vaccines Induce Targeted Epitope-Specific CTLs against Minor Histocompatibility Antigens from a Normal or Tolerized Repertoire J. Immunol., October 1, 2004; 173(7): 4492 - 4499. [Abstract] [Full Text] [PDF]
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R. A. K. Singh, J. R. Rodgers, and M. A. Barry The Role of T Cell Antagonism and Original Antigenic Sin in Genetic Immunization J. Immunol., December 15, 2002; 169(12): 6779 - 6786. [Abstract] [Full Text] [PDF]
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