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United States Department of Agriculture

Agricultural Research Service

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Research Project: Development of a Proof-of-Concept Rationally Designed Live Attenuated African Swine Fever Virus Vaccines

Location: Foreign Animal Disease Research

Project Number: 1940-32000-056-09
Project Type: Reimbursable

Start Date: Jan 01, 2011
End Date: Dec 30, 2014

Objective:
1. Develop recombinant African Swine Fever Virus (ASFV) strains by deletion of one or more viral genes already described as responsible for inducting attenuation of highly virulent ASF strains. 2. Test attenuated ASFV strains for their ability to induce protection against challenge with homologous, well-characterized, virulent ASFV isolates. 3. Evaluate patterns of heterologous protection among genetically heterogeneous ASFV strains. Amendment 1: 4. Development of recombinant Georgia ASFV (rG-ASFV) strains having deleted several of those genes previously identified to be involved in the production of attenuation of other virulent ASFV strains. 5. Develop an ASFV subunit experimental vaccine using modified vaccine Ankara (MVA) virus as a delivery vector.

Approach:
1. Develop recombinant African Swine Fever Virus (ASFV) strains by deletion of one or more viral genes already described as responsible for inducting attenuation of highly virulent ASF strains. Critical ASFV genes that are responsible for inducing attenuation of highly virulent ASF strains will be deleted individually or as a group. This deletion should confer virus replication but not disease production. 2. Test attenuated ASFV strains for their ability to induce protection against challenge with homologous, well-characterized, virulent ASFV isolates. This will be done through: Testing strains for in vivo attenuation, testing for efficacy against homologous challenge, determination of minim protective dose response, evaluation of protection profile for at least one attenuated ASFV vaccine candidate, and the evaluation of lead vaccine candidate to induce sterile immunity. 3. Evaluate and confirm cross-protection conferred by lead vaccine candidate (obj. 2) by using genetically diverse ASFV strains. 4. Standardize and optimize the use of the loxP/Cre system for sequential deletion to produce ASFV undergoing sequential recombination events allowing for the production of virus genome presenting multiple gene deletions. 5. The recombinant modified vaccine Ankara (MVA) will undergo immunogenicity testing. Animals will be inoculated with recombinant MVA (rMVA) expressing four immunogenic proteins of ASFV. The immune response and protection against challenge with the virulent parental ASFV will be assessed. Studies will also be conducted to assess the increase and stablization of the expression of ASFV proteins using rMVA as an expression vector. Based on the results obtained in initial studies described above, three different types of poxvirus promoters will be assessed for their ability to direct the expression of the ASFV proteins expressed in the rMVA. It is expected that a unique type of promoter will be selected for the development of rMVA in the near future.

Last Modified: 8/1/2014
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