Giuseppe
Emeritus
Virology. 2009 Aug 14. [Epub ahead of print]
High dose of plasmid IL-15 inhibits immune responses in an influenza non-human primates immunogenicity model.
Yin J, Dai A, Laddy DJ, Yan J, Arango T, Khan AS, Lewis MG, Andersen H, Kutzler MA, Draghia-Akli R, Weiner DB, Boyer JD. - Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 505 SCL, 422 Curie Blvd. Philadelphia, PA 19104, USA.
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(+) and CD8(+) T cells, as well as T(CM) levels in proliferating CD8(+) T cells (0.25 mg). Whereas, high doses of IL-15 (4 mg) decrease the production of IFN-gamma and the proliferation of CD4(+) and CD8(+) T cells and T(CM) levels in the proliferating CD4(+) and CD8(+) 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.
PMID: 19683780 [PubMed - as supplied by publisher]
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High dose of plasmid IL-15 inhibits immune responses in an influenza non-human primates immunogenicity model.
Yin J, Dai A, Laddy DJ, Yan J, Arango T, Khan AS, Lewis MG, Andersen H, Kutzler MA, Draghia-Akli R, Weiner DB, Boyer JD. - Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 505 SCL, 422 Curie Blvd. Philadelphia, PA 19104, USA.
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(+) and CD8(+) T cells, as well as T(CM) levels in proliferating CD8(+) T cells (0.25 mg). Whereas, high doses of IL-15 (4 mg) decrease the production of IFN-gamma and the proliferation of CD4(+) and CD8(+) T cells and T(CM) levels in the proliferating CD4(+) and CD8(+) 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.
PMID: 19683780 [PubMed - as supplied by publisher]
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