Title

Modulation of a PRRSV ORF7 DNA vaccine induced immune response in swine by co-delivery of cytokines

Date of Completion

January 2005

Keywords

Biology, Microbiology|Agriculture, Animal Pathology|Biology, Veterinary Science

Degree

Ph.D.

Abstract

This dissertation investigated the role played by interleukin 2 (IL-2) and interleukin 4 (IL-4) during the development of the immune response in swine. Because of their opposing regulatory effects, demonstrated primarily in mice, it was expected that these cytokines would modulate the immune response in swine toward either a Th1 or Th2 response respectively. Therefore, we compared these two cytokine as adjuvants of a DNA-based vaccine against porcine reproductive and respiratory syndrome virus (PRRSV). ^ The first section of this dissertation is a literature review that covers background information and the significance of this research and provides an outline of the specific aims. Chapter one, "Cloning and Characterization of a PRRSV Derived DNA Vaccine and a Swine IL-2 and Swine IL-4 Adjuvant Constructs" describes the cloning strategies and molecular and functional characterizations of the phCMV-ORF7 vaccine construct and the cytokine phCMV-IL2 and phCMV-IL4 constructs. This part of the study shows that the cloned constructs were correct and functionally active and therefore suitable to be used in the vaccination phase of the study. Chapter two, "Effects of Swine IL-2 and Swine 1L-4 on the Immune Responses Elicited by a PRRSV-ORF7 DNA Vaccine in Swine" describes the vaccination and challenge trial of the experimental animals. The effects of IL-2 and IL-4 on the vaccine-induced immune responses are described and discussed as well as the response to the homologous viral challenge. Portions of this chapter have been published in Veterinary Pathology and Immunopathology. The third and last chapter, "Pathologic and Immunohistochemical Study of Lungs from Pigs Immunized with a phCMV-ORF7 DNA Vaccine With or Without IL-2 or IL-4 and Challenged with Homologous Virus" describes and discusses the virus challenge and the gross and histopathology effects on the experimental animals, focusing in particular to the effects on the lungs. ^