1a.Objectives (from AD-416):
This research project seeks to address the threat of an introduction and subsequent outbreak of African Swine Fever (ASF) into the United States through a comprehensive research program aimed at countermeasure development. Specific objectives include:
1. Development of challenge model for ASF to characterize pathogenesis and evaluate novel countermeasure products.
2. Determine the immune mechanisms of protection induced by attenuated strains.
3. Determine the role of viral proteins in virulence/ pathogenesis/ protection through functional genomic analysis.
1b.Approach (from AD-416):
1. The development of a challenge model for ASF will be accomplished through challenging pigs with virulent ASFV via different routes (oral, nasal, and intramuscular) and at varying doses. The goal is to develop a system of viral challenge that accurately simulates natural infection. Model efficacy will be evaluated by characterizing viral dynamics in live animals and post-mortem samples.
2. The immune response to challenge with attenuated strains will be determined by analyzing the onset of protection. Comparative studies will be conducted using virulent and attenuated stratins focusing on temporal, anatomic and phenotypic characterization of ASFV distribution. Pro-inflammatory chemical mediators will be analyzed and cytotoxic T lymphocyte activity studied to determine mechanisms of immune response.
3. Bioinformatic analysis will be conducted on ASFV proteins to determine their role(s) in virulence/pathogenesis/ protection. Further analysis will be conducted to determine the host–virus interaction at the genomic level using microarray technology.
Two major areas were identified as priorities in this project: (i) the development of a model to evaluate vaccine potency for any putative ASFV experimental vaccine via a challenge model in swine, and (ii) the comparative study of virus pathogenesis induced by virulent verses attenuated virus strains. This study is designed to identify possible host immune mechanisms that can protect against the infection. Therefore, different routes of ASFV inoculation were tested using a variety of viral doses. The oronasal-nasopharyngeal route was characterized as the more superior route, as compared to nasaloropharyngeal inoculation and is more superior to intramuscular route because it more closely simulates natural infections; however, 3 routes (intramuscular, nasopharyngeal and contact) which all produced a systemic disease that, by its kinetics, clinical signs and lesions closely relates to the one described as natural infection. In addition, based on information produced in item (i) pathogenesis experiments have been performed which analyzed the differences in the infection and disease caused by highly virulent strain Malawi and an attenuated version of the same virus obtained by genetic manipulation. Primarily, basic experiments were performed detecting organs and tissues of active initial virus replication, and characterizing them in terms of virus yields.
No technologies were transferred in FY 2013. No publications were produced during FY 2013.