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High dose of plasmid IL-15 inhibits immune responses in an influenza non-human primates immunogenicity model
Journal article   Open access   Peer reviewed

High dose of plasmid IL-15 inhibits immune responses in an influenza non-human primates immunogenicity model

Jiangmei Yin, Anlan Dai, Dominick J Laddy, Jian Yan, Tatiana Arango, Amir S Khan, Mark G Lewis, Hanne Andersen, Michele A Kutzler, Ruxandra Draghia-Akli, …
Virology (New York, N.Y.), v 393(1), pp 49-55
2009
PMID: 19683780
url
https://doi.org/10.1016/j.virol.2009.07.017View
Published, Version of Record (VoR) Open

Abstract

IL-15 Influenza Vaccines
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-γ (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-γ 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.

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