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Originally published online as doi:10.1189/jlb.1004621 on April 7, 2005

Published online before print April 7, 2005
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(Journal of Leukocyte Biology. 2005;78:178-186.)
© 2005 by Society for Leukocyte Biology

Mucosal application of plasmid-encoded IL-15 sustains a highly protective anti-Herpes simplex virus immunity

Felix N. Toka*,{dagger} and Barry T. Rouse*,1

* Department of Microbiology, University of Tennessee, Knoxville; and
{dagger} Department of Preclinical Sciences, Immunology Laboratory, Faculty of Veterinary Medicine, Warsaw Agricultural University, Poland

1 Correspondence: Department of Microbiology, University of Tennessee, Walter’s Life Science Bldg. M409, 1414 Cumberland Ave., Knoxville, TN 37996. E-mail: btr{at}utk.edu

In a DNA immunization against Herpes simplex virus (HSV), we examined the ability of plasmid-encoded interleukin-15 (pIL-15) to induce and maintain the mucosal B and T cell immune response. pIL-15 generated memory CD8+ T cell responses that were threefold higher and mainly maintained in the spleen, but high levels of immunoglobulin A antibodies were induced and maintained long-term in the vaginal mucosa. Both of these enhanced components of the immune responses were recalled rapidly upon challenge with a lethal dose of HSV McKrae, affording protection in mice immunized with codelivery of pIL-15. Our results show for the first time that intranasal administration of pIL-15 along with plasmid-encoded glycoprotein B of HSV leads to enhancement of primary and memory CD8+ T cell responses as well as humoral immune response. Therefore, a mucosal immunization strategy that incorporates a potent cytokine such as IL-15 as an adjuvant might induce protective mucosal immune responses that constitute the initial barrier at mucosal portals of pathogen entry.

Key Words: HSV • CD8+ T cells • IgG • IgA




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