title: High dose of plasmid IL-15 inhibits immune responses in an influenza non-human primates immunogenicity model.
abstract: 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 505 SCL, 422 Curie Blvd. Philadelphia, PA 19104, USA.
authors.forename: Jiangmei
authors.initials: J
authors.lastname: Yin
authors.forename: Anlan
authors.initials: A
authors.lastname: Dai
authors.forename: Dominick J
authors.initials: DJ
authors.lastname: Laddy
authors.forename: Jian
authors.initials: J
authors.lastname: Yan
authors.forename: Tatiana
authors.initials: T
authors.lastname: Arango
authors.forename: Amir S
authors.initials: AS
authors.lastname: Khan
authors.forename: Mark G
authors.initials: MG
authors.lastname: Lewis
authors.forename: Hanne
authors.initials: H
authors.lastname: Andersen
authors.forename: Michele A
authors.initials: MA
authors.lastname: Kutzler
authors.forename: Ruxandra
authors.initials: R
authors.lastname: Draghia-Akli
authors.forename: David B
authors.initials: DB
authors.lastname: Weiner
authors.forename: Jean D
authors.initials: JD
authors.lastname: Boyer
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D004305:Dose-Response Relationship, Drug; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007252:Influenza Vaccines / Q000235:genetics / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D019409:Interleukin-15 / Q000235:genetics / Q000276:immunology*; D008253:Macaca mulatta; D010957:Plasmids; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; D019409:Interleukin-15; D019444:Vaccines, DNA; D007371:Interferon-gamma
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