Location: Virus and Prion Research
Project Number: 5030-32000-108-00-D
Project Type: Appropriated
Start Date: Oct 19, 2011
End Date: Oct 18, 2016
Objective 1: Identify mechanisms of porcine respiratory and reproductive syndrome virus (PRRSV) pathogenesis and develop vaccination strategies to enhance immunity and prevent the infection of swine herds. Subobjective 1.1: Identify PRRSV determinants of viral pathogenesis, immune evasion, and transmission. Subobjective 1.2: Use reverse genetic technology to design live attenuated vaccine strains that provide broad protection against PRRSV infection and allow differentiation of infected from vaccinated animals. Objective 2: Identify mechanisms of swine influenza virus (SIV) pathogenesis and develop vaccination strategies that provide broad cross-protection against subtypes of SIV that are emerging worldwide. Subobjective 2.1: Improve SIV vaccination and control programs through development of a repository of characterized emerging SIV subtypes and genotypes. Subobjective 2.2: Determine the role of the triple reassortant internal gene cassette (TRIG) or other genetic elements in the adaptation of novel reassortant influenza viruses to pigs. Subobjective 2.3: Discover novel influenza vaccine platforms that elicit cross-protection against emerging SIV subtypes. Objective 3: Identify viral factors contributing to porcine circovirus associated disease (PCVAD) complex and develop novel vaccination strategies to enhance the protection of swine herds. Subobjective 3.1: Identify unique endemic or novel swine viruses that are associated with PCVAD. Subobjective 3.2: Determine the role of these viruses, including PCV2, in inducing PCVAD. Subobjective 3.3: Discover novel vaccine platforms designed to improve control and prevention of PCVAD. Objective 4: Develop methods to modulate innate and adaptive immune responses to swine viral pathogens. Subobjective 4.1: Identify innate defense mechanisms associated with disease resistance to viral pathogens. Subobjective 4.2: Discover novel biotherapeutics or other intervention strategies to ameliorate the effects of diseases caused by priority viral diseases of swine. Objective 5. Identify mechanisms of pathogenesis, transmission, and immunity for coronaviruses including Porcine Epidemic Diarrhea Virus (PEDV) and other emerging viral diseases of swine. Subobjective 5.1: Identify mechanisms of PEDV pathogenesis in neonatal pigs. Subobjective 5.2: Identify susceptible hosts and mechanisms of PEDV transmission. Subobjective 5.3: Identify immune responses to PEDV infections, including the ontogeny and mechanisms of protective immunity associated with maternally derived antibodies. Subobjective 5.4: Identify mechanisms of protective immunity in neonatal and adult pigs. Objective 6: Develop countermeasures to predict, prevent and control disease outbreaks caused by emerging coronaviruses of swine. Subobjective 6.1: Identify viral molecular determinants of virulence of emerging coronaviruses. Subobjective 6.2: Discover and assess PEDV vaccine platforms that induce effective lactogenic immunity. Subobjective 6.3: Discover and assess PEDV vaccine platforms that can override maternal antibody interference in neonatal pigs and prevent transmission in adult pigs.
The pathogenesis of disease caused by swine viral pathogens will be investigated in swine disease models to investigate methods of intervention. Animal experiments conducted involve one of four general designs: 1) disease pathogenesis and transmission studies, 2) vaccine efficacy studies, 3) neonatal studies, and 4) a gnotobiotic model in sterile-filtered pig isolators to study the effects of a single pathogen on the pig. Knowledge obtained will be applied to break the cycle of transmission of these swine pathogens through development of better vaccines or other novel intervention strategies. A major research approach will be the use of reverse engineering and infectious clones to identify virulence components of each virus under study through mutational studies. Development of vaccines that provide better cross-protective immunity than what is currently available with today’s vaccines will be approached through vaccine vector platform development, attenuated strains for vaccines and other novel technologies. A key approach in the study of disease pathogenesis is to better understand the host response to viral infection to various viruses. This research on comparative host transcriptomics will provide insights on viral pathogenesis and possible virulence factors that will enable rational design of more effective vaccines and target possible novel intervention strategies.