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Principal Investigator: Dr. Julia Flaminio
Contact Information: Email: mbf6@cornell.edu - Phone: 3-3119
Sponsor: President's Council of Cornell Women
Title: The Effect of CpG-ODN on The Antigen Presenting Cells of Foals
Annual Direct Cost: $11,810
Project Period: 6/1/04-5/31/05
The main objective of this proposal is to test the effect of an adjuvant called cytosine-phosphate-guanosine oligodeoxynucleotide (CpG-ODN) in the immune response of equine neonate. More specifically, we are interested in the effect of CpG-ODN on monocyte-derived macrophages and dendritic cells from foals of different ages (from birth to 4 months of age) in comparison to adult horses. These data will be essential for the design of subsequent in vivo studies using CpG-ODN in vaccine products for the protection against viruses and intracellular bacteria. Our long-term goal is to develop vaccination strategies that can be used in foals immediately after birth for the protection against diseases that present a threat in the first few months of life.
Many commercially available vaccines contain a fraction of inactivated virus or bacterium in combination with an adjuvant. The purified organism determines the specificity of the immune response. However, the inactivated organism on its own cannot trigger the desired immune-recognition and response. These objectives may be achieved with the addition of an adjuvant, which is a substance that promotes the attraction and activation of immune cells that recognize and process foreign particles (antigens).
CpG-ODN motifs have been studied for their application as adjuvants in vaccines, more importantly in neonate vertebrates (Klinman, 2003). Short, synthetic CpG-ODNs mimic bacterial DNA, and they can induce B cell proliferation and antibody production, macrophage activation, and dendritic cell maturation in vitro (Krieg et al., 2002). In vivo, they induce strong Th1 responses, with both cellular and humoral components (Ballas et al., 1996; Maletto et al., 2002). This type of immune response is essential for the protection against viral and intracellular bacterial organisms, including the Rhodococcus equi bacterium, which presents a threat to foals distinctively from birth to 5 months of age.
Our preliminary data show that foal mononuclear cells do respond to CpG-ODN motifs, and CpG-ODNs could potentially serve as an adjuvant to promote effective antigen recognition, processing and presentation by antigen presenting cells in the newborn foal. Using similar assays described by Rankin et al. (1999), we asked if foal cells would be capable of recognizing the optimal CpG-ODN sequence for the horse. Isolated mononuclear cells from peripheral blood of 2-day-old foals (n = 9) and from a 5-day-old foal lymph node (n = 1) did respond to this specific CpG-ODN in the presence or absence of antigens. These results support the design of additional experiments to study the CpG-ODN effect on antigen presenting cells of foals. Based on this preliminary data, there is a possibility that CpG-ODN will function as an adjuvant to augment antigen processing and presentation by antigen presenting cells of foals immediately after birth.
To test the use of CpG-ODN as an adjuvant, the first step is to identify its effects on equine antigen presenting cells, which are the cells of the immune system that recognize and process antigens. To evaluate the effects of CpG-ODN in the immune cells of the foal, we will examine the expression of cell surface activation markers, and immune mediators (cytokines) in cells cultured with this adjuvant.
If the findings in the horse agree with the findings in other species, CpG-ODNs may have important applications in the design of vaccines against viruses and intracellular bacteria that pose a threat to foals' health in early life.
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