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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.

journal_name

Virology

journal_title

Virology

authors

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

doi

10.1016/j.virol.2009.07.017

subject

Has Abstract

pub_date

2009-10-10 00:00:00

pages

49-55

issue

1

eissn

0042-6822

issn

1096-0341

pii

S0042-6822(09)00424-3

journal_volume

393

pub_type

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