Affiliation:
1. Division of Microbiology and Immunology, Yerkes National Primate Research Center and Vaccine Research Center of Emory University School of Medicine, Atlanta, Georgia 30329
2. Oncology Center, School of Medicine, The Johns Hopkins University, Baltimore, Maryland 21231
Abstract
ABSTRACT
Interferon regulatory factor 1 (IRF-1), IRF-3, and IRF-7 have been tested as genetic adjuvants for influenza virus hemagglutinin (HA) and nucleoprotein vaccine DNAs. Cotransfection of HA with IRF-3 and IRF-7 increased CD4 T-cell responses by 2- to 4-fold and CD8 T-cell responses by more than 10-fold. Following intramuscular deliveries of DNA, both CD4 and CD8 T cells were biased towards type 1 immune responses and the production of gamma interferon. Following gene gun bombardments of DNA, both were biased towards type 2 immune responses and the production of interleukin-4. The biases of the T-cell responses towards type 1 or type 2 were stronger for immunizations with IRF-3 as an adjuvant than for immunizations with IRF-7 as an adjuvant. Moderate adjuvant effects for antibody were observed. The isotypes of the antibody responses reflected the method of DNA delivery; intramuscular deliveries of DNA predominantly raised immunoglobulin G2a (IgG2a), whereas gene gun deliveries of DNA predominantly raised IgG1. These biases were enhanced by the codelivered IRFs. Overall, under the conditions of our experiments, IRF-3 had good activity for T cells, IRF-7 had good activity for both antibody and T cells, and IRF-1 had good activity for antibody.
Publisher
American Society for Microbiology
Subject
Virology,Insect Science,Immunology,Microbiology
Reference40 articles.
1. Au, W. C., P. A. Moore, D. W. LaFleur, B. Tombal, and P. M. Pitha. 1998. Characterization of the interferon regulatory factor-7 and its potential role in the transcription activation of interferon A genes. J. Biol. Chem. 273 : 29210-29217.
2. Au, W. C., P. A. Moore, W. Lowther, Y. T. Juang, and P. M. Pitha. 1995. Identification of a member of the interferon regulatory factor family that binds to the interferon-stimulated response element and activates expression of interferon-induced genes. Proc. Natl. Acad. Sci. USA 92 : 11657-11661.
3. Functional Analysis of Human Herpesvirus 8-Encoded Viral Interferon Regulatory Factor 1 and Its Association with Cellular Interferon Regulatory Factors and p300
4. Cohen, A. D., J. D. Boyer, and D. B. Weiner. 1998. Modulating the immune response to genetic immunization. FASEB J. 12 : 1611-1626.
5. Deng, Y., J. W. Yewdell, L. C. Eisenlohr, and J. R. Bennink. 1997. MHC affinity, peptide liberation, T cell repertoire, and immunodominance all contribute to the paucity of MHC class I-restricted peptides recognized by antiviral CTL. J. Immunol. 158 : 1507-1515.
Cited by
64 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