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Title: IN VITRO STUDIES ON THE IMMUNOMODULATORY EFFECTS OF CPG MOTIFS AS POTENTIAL VACCINE ADJUVANTS

Author
item XIE, H - UNIV. OF MARYLAND
item RAYBOURNE, R - FDA
item BABU, U - FDA
item Lillehoj, Hyun
item HECKERT, R - FDA

Submitted to: Poultry Science Association Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 5/1/2002
Publication Date: N/A
Citation: N/A

Interpretive Summary:

Technical Abstract: Bacterial DNA has been found to be able to activate cells of the immune system. This property is due to the fact that bacterial DNA is rich in unmethylated CpG repeats that occur at very low frequencies in the vertebrates. Synthetic unmethylated CpG oligonucleatide sequences (ODNs) can mimic the immunostimulatory activity of bacterial DNA, and modulate immune responses of cells including macrophages/monocytes, natural killer cells, dendritic cells, and lymphocytes. CpG-ODNs induced increased proinflammatory cytokine production, up-regulated cell surface antigen expression, and enhanced cell proliferation in mammalian models. In vivo studies also suggested that CpG-ODNs could be used as adjuvants for vaccines against various pathogens including bacteria and parasites. However, very limited information is available on the role of CpG-ODNs in poultry system. In the current study, a number of CpG-ODNs with optimal stimulatory activity in humans and mice have been tested on chicken macrophage cell line HD 11 cells. Preliminary results showed thatcertain CpG-ODNs show interesting effects on chicken cells as in the mammalian system.A CpG-ODN designated as "HuI"which is stimulatory for humans,also induced strong IL-6 and nitric oxide secretion in cultured a chicken macrophage cell line, HD 11, in dose- and time-dependent manners. HuI also increased anintracellular killing of S. enteritidis (SE) by HD 11 cells. On the other hand, unlike its effect on human cells, HuI reduced proliferation and induced apoptosis of HD11 cells.HuI-induced apotosis was blocked by NG-monomethyl L-arginine (L-NMMA), an inducible nitric oxide synthase (iNOS) inhibitor, suggesting that HuI induced apoptosis in HD 11 cells is likely through an iNOS-dependent pathway. In summary, CpG- induced INOS activityand apoptosis of HD11 cells maylead to the increased intracellular killing activity of SE in HD 11 cells. These results also indicate that there are species-related differences in to the activity of CpG-ODNs, and CpG-ODNs have potential as vaccine adjuvants in poultry.