Project Number: 3625-32000-089-00
Project Type: Appropriated

Start Date: Jan 16, 2007
End Date: Oct 05, 2011

Objective:
1. Characterize mechanisms of respiratory disease infections by defining determinants of virulence and respiratory pathogen interactions that lead to polymicrobial infections. 2. Characterize changes in host-pathogen gene expression that are associated with the PRDC. 3. Design novel vaccine approaches for swine respiratory pathogens of interest, using bacterial ghost technology, and assess their safety and efficacy in validated PRDC disease models.

Approach:
Objective 1: Identifying the contribution of the different pathogens involved in porcine respiratory disease is important in understanding the complex. We will characterize and compare the ability of the bacterial and viral pathogens involved in PRDC to act alone and in concert to exacerbate disease. These studies will involve developing in vivo porcine animal models of single and mixed infections involving PRDC pathogens and determining important interactions among these agents. Subobjective 1.2 describes plans to investigate the role of putative virulence factors of PRDC bacterial pathogens through the generation of mutants and in vitro and in vivo functional testing of these mutants. Objective 2: Infected hosts recognize the presence of pathogens and mobilize specific immune defense mechanisms. Pathogens in turn can actively modulate host-signaling and immune-pathways to enhance their persistence and survival. Global networks for gene regulation in bacteria allow these organisms to adapt to different environmental niches and host microenvironments; such adaptation underlies the capacity of infectious agents to persist in and damage host tissues. We plan to perform comprehensive profiling of the transcriptional response of both the host, porcine respiratory tract, and the pathogen, Bordetella bronchiseptica, by exploiting two approaches. First, using a B. bronchiseptica microarray, we will analyze the global expression profile of B. bronchiseptica during various in vitro growth conditions and during respiratory tract infections. Secondly, utilizing tissue samples from the previously mentioned infection models and a porcine immune microarray, we will thoroughly investigate the immune response pathways that underlie respiratory infections. Objective 3: Improved vaccines for swine respiratory disease agents are needed. Commercially available products sometimes fail to provide reliable protection against disease, are costly, and cumbersome to administer, and retain undesirable side-effects. We will determine the efficacy of bacterial ghosts (BG) as vaccines against respiratory pathogens of swine in our swine respiratory infection models. BSL-Exempt; Recertified 10/16/10 #0205. BSL-2; Recertified 10/16/10 #207. BSL-Exempt; Recertified 10/17/10 #0208. BSL-2; Recertified 10/20/10 #0232. BSL-2; Recertified 10/17/10 #0233. BSL-2; Recertified 10/17/10 #0234. BSL-Exempt; Recertified 10/17/10 #0235. BSL-Exempt; Recertified 10/17/10 #0240. BSL-2; Recertified 10/17/10 #0245. BSL-Exempt; Cancelled 8/10/07 #0267. BSL-2; Recertified 1/13/11 #0283. BSL-2; Recertified 2/18/11 #0299. BSL-2; Certified 08/16/10 #0333. BSL-2; Certified 10/01/10 #0336. BSL-2; Certified 12/13/10 #0337. BSL-2; Certified 12/13/10 #0338. BSL-2; Certified 12/13/10 #0340.