ARS | Publication request: Biotherapeutics as alternatives to antibiotics: effects of IFN-a and G-CSF on innate and adaptive immunity in swine

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: June 16, 2012
Publication Date: N/A

Technical Abstract: Acceptable alternatives to the use of antibiotics in food animal practice need to be explored. The use of immunomodulators is a promising area for therapeutic, prophylactic, and metaphylactic use to prevent and combat infectious disease during periods of peak disease incidence. We developed a method to circumvent the need for production of a recombinant cytokine by using a replication-defective adenovirus vector that expresses interferon-alpha (IFN-alpha) or porcine granulocyte colony-stimulating factor (G-CSF). Type I interferons, such as IFN-alpha, contribute to innate antiviral immunity by promoting production of antiviral mediators and also play a role in the adaptive immune response. G-CSF enhances neutrophil production and release from the bone marrow and is already licensed for use in humans for treatment of neutropenia and prevention of infections in those with compromised immunity such as chemotherapy patients. Its prophylactic use has also been experimentally shown to reduce the incidence of coliform and staphylococcal mastitis in cows. Porcine reproductive and respiratory syndrome virus (PRRSV) causes one of the most devastating and costly diseases to the swine industry world-wide and has been shown to induce a meager interferon IFN-alpha response. Pigs administered the vector expressing porcine IFN-alpha and challenged with PRRSV had lower febrile responses and decreased percentage of lung involvement. Viremia was delayed and there was a decrease in viral load in the sera of pigs. In addition, there was an increase in the number of virus-specific IFN-gamma secreting cells, as well as an altered cytokine profile in the lung 14 days post-infection, indicating that the presence of IFN-alpha at the time of infection can alter innate and adaptive immune responses to PRRSV. These results indicate that IFN-alpha can have protective effects if present during the time of infection with PRRSV. Intramuscular administration of the vector expressing porcine G-CSF was found to elicit 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 prevention or treatment of infectious disease, especially during typical times of stress and pathogen exposure such as post-weaning and post partum.