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The Journal of Immunology, Vol 155, Issue 1 259-265, Copyright © 1995 by American Association of Immunologists
ARTICLES |
E Manickan, RJ Rouse, Z Yu, WS Wire and BT Rouse
Department of Microbiology, College of Veterinary Medicine, University of Tennessee, Knoxville 37996, USA.
Plasmid DNA encoding proteins represent a convenient novel approach to vaccination. We have investigated this "genetic immunization" approach as a means to protect against herpes simplex virus (HSV) infection using a mouse zosteriform model that mimics several aspects of reactivated HSV infection of humans. After i.m. immunization with plasmid DNA-encoding glycoprotein B (gB), (pc-gB), 80% of BALB/c mice were completely protected and lesions were delayed in the remaining animals. Upon pc-gB vaccination, the animals developed both gB- and HSV- specific IgG Ab response and the isotype examination revealed a predominance of IgG2a. These mice also have low levels (1/16) of HSV- neutralizing Abs. Immune splenocytes obtained from pc-gB-immunized mice, when restimulated in vitro with HSV resulted in production of type 1 cytokines. Evidence for CD(8+)-mediated cytotoxic T lymphocyte response was equivocal. Protection could be adoptively transferred to nude mice recipients by CD4+ T cells from pc-gB-immunized mice but not by CD8+ T cells. Our results demonstrate that genetic immunization is a potent means of inducing protection against HSV and that the mechanism of immunity responsible for clearing virus from cutaneous sites is principally by CD4+ T cells. It is likely that these cells are Th1 cells because type 1 cytokines were the major cytokines detected upon in vitro Ag stimulation.
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M. J. Hariharan, D. A. Driver, K. Townsend, D. Brumm, J. M. Polo, B. A. Belli, D. J. Catton, D. Hsu, D. Mittelstaedt, J. E. McCormack, et al. DNA Immunization against Herpes Simplex Virus: Enhanced Efficacy Using a Sindbis Virus-Based Vector J. Virol., February 1, 1998; 72(2): 950 - 958. [Abstract] [Full Text] [PDF]
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Y.-H. Chow, B.-L. Chiang, Y.-L. Lee, W.-K. Chi, W.-C. Lin, Y.-T. Chen, and M.-H. Tao Development of Th1 and Th2 Populations and the Nature of Immune Responses to Hepatitis B Virus DNA Vaccines Can Be Modulated by Codelivery of Various Cytokine Genes J. Immunol., February 1, 1998; 160(3): 1320 - 1329. [Abstract] [Full Text] [PDF]
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