Submitted to: American Veterinary Medical Association Abstract
Publication Type: Abstract Only
Publication Acceptance Date: May 1, 2013
Publication Date: July 19, 2013
Citation: Loving, C.L. 2013. Biotherapeutics as alternatives to antibiotics. 2013 American Veterinary Medical Association (AVMA) Annual Convention, July 19-23, 2013, Chicago, Illinois. Paper No. 13906. Technical Abstract: Increasing pressure to limit antibiotic use in agriculture is heightening the need for alternative methods to reduce the adverse effects of clinical and subclinical disease on livestock performance that are currently managed by in-feed antibiotic usage. Immunomodulators have long been sought as such a method for therapeutic, prophylactic or metaphylactic approaches in livestock to prevent and combat infectious disease during periods of peak disease incidence. In humans, granulocyte colony stimulatory factor (G CSF) is used to reduce the risk of respiratory infections associated with compromised immunity in chemotherapy patients. G-CSF is a cytokine that controls the normal daily production, differentiation, and function of granulocytes from the bone marrow. Previous studies with G-CSF administration in cattle have shown significant enhancement of disease resistance against various bacterial pathogens including but not limited to Staphylococcus aureus, Escherichia coli and Klebsiellia pneumonia, as well as respiratory pathogens. However, a limitation of a biotherapeutic cytokine such as G-CSF, is the very short half-life resulting in a short duration of effectiveness thus limiting their practical use as a one-time injectable in production animal medicine. To address this issue, we developed a method to circumvent the need for production of a recombinant cytokine and the short half-life limitation by using a replication-defective adenovirus vector that expresses porcine G-CSF. Intramuscular administration of this vector expressing porcine G-CSF was found to effect a substantial persistent neutrophilia of at least 3 weeks duration. These findings provide evidence that it is possible to deliver G-CSF to have a sustained increase in circulating neutrophil numbers in pigs that may be a useful alternative to antibiotics for prophylactic or metaphylactic control of various bacterial pathogens associated with swine diseases. This presentation will summarize studies evaluating the effects of this type of biotherapeutic on respiratory and enteric pathogens in pigs.