High dose of plasmid IL-15 inhibits immune responses in an influenza non-human primates immunogenicity model
- Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 505 SCL, 422 Curie Blvd. Philadelphia, PA 19104 (United States)
- VGX Pharmaceuticals, Inc., The Woodlands, TX 77381 (United States)
- Research Section, Bioqual, Rockville, MD 20850 (United States)
- Drexel University College of Medicine, Philadelphia, PA 19102 (United States)
Interleukin (IL)-15, is a cytokine that is important for the maintenance of long-lasting, high-avidity T cell response to invading pathogens and has, therefore, been used in vaccine and therapeutic platforms as an adjuvant. In addition to pure protein delivery, plasmids encoding the IL-15 gene have been utilized. However, it is critical to determine the appropriate dose to maximize the adjuvanting effects. We immunized rhesus macaques with different doses of IL-15 expressing plasmid in an influenza non-human primate immunogenicity model. We found that co-immunization of rhesus macaques with a Flu DNA-based vaccine and low doses of plasmid encoding macaque IL-15 enhanced the production of IFN-gamma (0.5 mg) and the proliferation of CD4{sup +} and CD8{sup +} T cells, as well as T{sub CM} levels in proliferating CD8{sup +} T cells (0.25 mg). Whereas, high doses of IL-15 (4 mg) decrease the production of IFN-gamma and the proliferation of CD4{sup +} and CD8{sup +} T cells and T{sub CM} levels in the proliferating CD4{sup +} and CD8{sup +} T cells. In addition, the data of hemagglutination inhibition (HI) antibody titer suggest that although not significantly different, there appears to be a slight increase in antibodies at lower doses of IL-15. Importantly, however, the higher doses of IL-15 decrease the antibody levels significantly. This study demonstrates the importance of optimizing DNA-based cytokine adjuvants.
- OSTI ID:
- 21357543
- Journal Information:
- Virology, Journal Name: Virology Journal Issue: 1 Vol. 393; ISSN VIRLAX; ISSN 0042-6822
- Country of Publication:
- United States
- Language:
- English
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