A Human T-Cell Leukemia Virus Type 1 Regulatory Element Enhances the Immunogenicity of Human Immunodeficiency Virus Type 1 DNA Vaccines in Mice and Nonhuman Primates
-
Published:2005-07
Issue:14
Volume:79
Page:8828-8834
-
ISSN:0022-538X
-
Container-title:Journal of Virology
-
language:en
-
Short-container-title:J Virol
Author:
Barouch Dan H.1, Yang Zhi-yong2, Kong Wing-pui2, Korioth-Schmitz Birgit1, Sumida Shawn M.1, Truitt Diana M.1, Kishko Michael G.1, Arthur Janelle C.1, Miura Ayako1, Mascola John R.2, Letvin Norman L.1, Nabel Gary J.2
Affiliation:
1. Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215 2. Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, Maryland 20892-3005
Abstract
ABSTRACT
Plasmid DNA vaccines elicit potent and protective immune responses in numerous small-animal models of infectious diseases. However, their immunogenicity in primates appears less potent. Here we investigate a novel approach that optimizes regulatory elements in the plasmid backbone to improve the immunogenicity of DNA vaccines. Among various regions analyzed, we found that the addition of a regulatory sequence from the R region of the long terminal repeat from human T-cell leukemia virus type 1 (HTLV-1) to the cytomegalovirus (CMV) enhancer/promoter increased transgene expression 5- to 10-fold and improved cellular immune responses to human immunodeficiency virus type 1 (HIV-1) antigens. In cynomolgus monkeys, DNA vaccines containing the CMV enhancer/promoter with the HTLV-1 R region (CMV/R) induced markedly higher cellular immune responses to HIV-1 Env from clades A, B, and C and to HIV-1 Gag-Pol-Nef compared with the parental DNA vaccines. These data demonstrate that optimization of specific regulatory elements can substantially improve the immunogenicity of DNA vaccines encoding multiple antigens in small animals and in nonhuman primates. This strategy could therefore be explored as a potential method to enhance DNA vaccine immunogenicity in humans.
Publisher
American Society for Microbiology
Subject
Virology,Insect Science,Immunology,Microbiology
Reference40 articles.
1. Control of a Mucosal Challenge and Prevention of AIDS by a Multiprotein DNA/MVA Vaccine 2. Attal, J., M. C. Theron, F. Taboit, M. Cajero-Juarez, G. Kann, P. Bolifraud, and L. M. Houdebine. 1996. The RU5 (′R') region from human leukaemia viruses (HTLV-1) contains an internal ribosome entry site (IRES)-like sequence. FEBS Lett.392:220-224. 3. Barouch, D. H., S. Santra, T. D. Steenbeke, X. X. Zheng, H. C. Perry, M.-E. Davies, D. C. Freed, A. Craiu, T. B. Strom, J. W. Shiver, and N. L. Letvin. 1998. Augmentation and suppression of immune responses to an HIV-1 DNA vaccine by plasmid cytokine/Ig administration. J. Immunol.161:1875-1882. 4. Barouch, D. H., S. Santra, J. E. Schmitz, M. J. Kuroda, T.-M. Fu, W. Wagner, M. Bilska, A. Craiu, X. X. Zheng, G. R. Krivulka, K. Beaudry, M. A. Lifton, C. E. Nickerson, W. L. Trigona, K. Punt, D. C. Freed, L. Guan, S. Dubey, D. Casimiro, A. Simon, M.-E. Davies, M. Chastain, T. B. Strom, R. S. Gelman, D. C. Montefiori, M. G. Lewis, E. A. Emini, J. W. Shiver, and N. L. Letvin. 2000. Control of viremia and prevention of clinical AIDS in rhesus monkeys by cytokine-augmented DNA vaccination. Science290:486-492. 5. Barouch, D. H., S. Santra, K. Tenner-Racz, P. Racz, M. J. Kuroda, J. E. Schmitz, S. S. Jackson, M. A. Lifton, D. C. Freed, H. C. Perry, M. E. Davies, J. W. Shiver, and N. L. Letvin. 2002. Potent CD4+ T cell responses elicited by a bicistronic HIV-1 DNA vaccine expressing gp120 and GM-CSF. J. Immunol.168:562-568.
Cited by
147 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|