2013 Annual Report
1a.Objectives (from AD-416):
1. Develop intervention strategies to control and eradicate CSF virus by determining immune mechanisms mediating early protection and its application in blocking infection and preventing transmission and by discovering effective CSF vaccine and diagnostic platforms specifically designed for disease control and eradication.
2. Develop intervention strategies to control ASF virus by identifying virus-host determinants of virulence and transmission and by developing technologies to enable the development of ASF vaccines that are efficacious against the most prevalent ASF strains.
1b.Approach (from AD-416):
To develop strategies to control CSF virus and further vaccine and diagnostic platforms, improvements and further assessment will be conducted on ARS, PIADC previously developed live attenuated candidate marker vaccine strain (FlagT4v); inclusive of minimal protective dose response, toxicity, antibody response and genetic stability assessments. Studies will focus on protective innate immune mechanisms induced in swine after vaccination with live attenuated CSFV vaccine strains. Evaluation of native and modified forms of CSFV envelope proteins to analyze their capacity to induce rapid protective immune responses against infection with CSFV as a preliminary step in development of fast acting subunit marker vaccines.
Development of intervention strategies to control ASF virus will be done by identifying virus-host determinants of virulence and transmission and by developing technologies to enable the development of ASF vaccines that are efficacious against the most prevalent ASF strains. In vivo experimental models to study ASFV pathogenesis and host immune response in swine will be developed. Studies will focus on minimal lethal dose percentages, and early pathogenesis model with a virulent ASFV. The critical pathogenic and immunological mechanisms leading to protection against ASF will be identified. Technologies will be developed to enable the production of live attenuated vaccines for ASF.
During FY 2013 we started our work on ASF. Two major areas were identified as priorities: (i) the development of attenuated viruses, by genetic manipulation, to be used as experimental vaccines, and (ii) the comparative study of virus pathogenesis induced by virulent VS attenuated virus strains. Several recombinant viruses are under development based on the use of the highly virulent strain Georgia. Several specific viral genes, previously associated with virus attenuation, are being selectively deleted from the virus genome. The degree of attenuation of the resulting deletion virus mutants will be tested in swine. It is expected that some of these mutant viruses will be enough attenuated so they may be used as experimental vaccines. In addition, pathogenesis experiments are being performed analyzing differences in the infection caused by highly virulent strain Malawi and an attenuated version of the same virus obtained by genetic manipulation. Initially, basic experiments were performed testing different infectious routes and virus detection system.
Development of a companion diagnostic test to Classical Swine Fever (CSF) FlagT4 Vaccine. There is a need to develop a novel version of the DIVA test to differentiate animals immunized with CSF FlagT4 from animals infected with wild type CSFV strain. ARS researchers at Greenport, New York in collaboration with APHIS, PIADC have developed a new version of the test which allows the detection of most vaccinated animals from others infected with virulent CSFV. This test, after undergoing necessary validation, will be useful in controlling outbreak events and reduce the amount of slaughtered animals.
Evaluation of FlagT4 as a potential vaccine. To utilize the Classical Swine Fever Virus FlagT4 vaccine, ARS researchers at Greenport, New York conducted the analysis of FlagT4 vaccine candidate utilizing OIE standards; focusing on the minimal protective doses, toxicity assessment and an assessment of the degree of genetic instability. Results indicate that this vaccine candidate requires further research to address issues of genetic stability. FlagT4 is currently undergoing further review by a CRADA partner for commercialization.