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.
The goal of this interagency agreement is to develop countermeasure strategies against the introduction of African Swine Fever Virus (ASFV). ASF is endemic in Africa, Asia and Europe, and although currently disease free, the United States faces an increased risk through international commerce. We aim to identify the role of viral proteins in the induction of the antibody and cell mediated immunity in different ASF strains to aid in further vaccine development efforts.
In FY 2012 efforts began and will continue into FY 2013 in the following areas; the optimization of the detection of ASFV from tissues, blood and secretions and begin the characterization of the temporal dynamics of controlled direct inoculation of pigs with ASFV via oronasal and intramuscular routes. We will investigate the onset of protection after the infection with the attenuated virus strain. An analysis of the tissues and cell types involved in early replication of the attenuated vaccine strains compared with virulent parental ASFV will be conducted. Bioinformatic analysis of the protein function in the virulence/pathogenesis/protection processes will be conducted.