Dr. Julia Flaminio
Objectives of this Proposal:
The main objective of this proposal is to test the effect of an adjuvant called cytosine-phosphate-guanosine oligodeoxynucleotide (CpG-ODN) in the immune cells of young foals. This adjuvant has been used successfully to induce immune responses against viral and intracellular organisms in neonates and adults of many species. We are interested in its effect on antigen-presenting cells, and whether it can be used to influence the relative maturation status of these cells in foals. To test this question, we will examine the effect of CpG-ODNs on the expression of cell surface activation markers, and immune mediators (cytokines and intracellular proteins) in cells cultured with this adjuvant. The absence of a full response may characterize a relative impairment ('immaturity') in these foal cells with respect to function. A vigorous response, on the other hand, would suggest that CpG-ODNs may have important applications in the design of vaccines against viruses and intracellular bacteria that create a threat to foals health in early life.
Importance for the Horse Industry:
Vaccination is an important component of many programs for the prevention of infection. An efficacious vaccine is the one that induces a protective, long-lived immune response before the encounter with the pathogen. Many commercially available vaccines contain an inactive protein of the organism in combination with an adjuvant. The purified protein of the organism determines the specificity of the immune response. However, the protein on its own cannot trigger the desired immune-recognition and response. These objectives may be achieved by the use of an adjuvant, a substance that promotes the attraction and activation of immune cells that recognize and process foreign particles (antigens). These cells, also called antigen presenting cells (APCs), are important coordinators of the type of immune response to the antigen they encounter.
Although most parts of the immune system of the horse develops during fetal life, foals are very susceptible to infection within the first 5 months of age. Their susceptibility to infection in the neonatal period is partially dependent on the adequacy of transfer of maternally-derived antibodies through the colostrum. The horse placenta does not allow transfer of antibodies during gestation; hence the foal is born essentially devoid of antibodies. The maternally-derived antibodies absorbed in the first few hours of life confer short-lived, limited protection to the foal against environmental pathogens for the initial 1 to 2 months of life. After this period, the maternal antibodies reduce to very low levels, and the foal must depend on its own antibody production to resist infections.
The earlier the foal can assemble its own immune system to fight infection, the more resistant it will be to disease. Conversely, the less mature the immune system, the more susceptible it will be to pathogenic and opportunistic organisms in the environment. Some organisms may take advantage of the immature elements of the immune system of the foal to cause disease. For instance, Rhodococcus equi is an intracellular bacterium that causes pneumonia in foals up to 5-6 months of age. After this period, foals are not susceptible to the organism and do not develop pneumonia. The susceptibility to Rhodococcus equi precisely in early life suggests that some segments of the immune system of the foal are missing in early age. Conventional vaccines for Rhodococcus equi have been designed and tested, but result in only marginal protection early in life. Therefore, the identification of an effective means to augment the immune system of foals soon after birth would reduce the period of susceptibility to pathogenic organisms, and the chances of disease. Thus, the purpose of this project is to determine if CpG-ODN may assist foals in the maturation of their immune system.