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Research Project: Analysis of the Immune Response Elicited by Classical Swine Fever Virus Recombinant Vaccine Candidate FlagT4G

Location: Foreign Animal Disease Research

Project Number: 3022-32000-063-022-S
Project Type: Non-Assistance Cooperative Agreement

Start Date: Aug 1, 2020
End Date: Jul 31, 2025

Recombinant FlagT4G virus is a rationally developed Classical Swine Fever Virus (CSFV) vaccine candidate developed by ARS scientists. FlagT4G is a live attenuated virus harboring positive and antigenic markers which allow the serological differentiation between vaccinated and infected animals (DIVA markers). This vaccine induced an efficient protective immune response since day 3 post inoculation, a time where no virus specific antibody response is detected. Animals vaccinated with FlagT4G developed a strong adaptive antibody response after the third week post inoculation. Therefore, immune mechanisms mediating FlagT4G elicited early and late protection are not fully understood. This project proposes a systematic evaluation of the innate and adaptive immune mechanisms induced in FlagT4G inoculated animals. Amendment I: The project will be expanded to include the investigation of the importance of specific interactions between CSFV structural protein E2 and swine host proteins in the process of CSFV virulence in pigs. Amendment II: Expanded objective to include the study of Flagt4 virus in the induction of transplacentary transmission in pregnant swine.

ARS PIADC, NY, and CRESA, Barcelona, will conduct experiments aimed at the identification of the protective immune mechanisms elicited by FlagT4G. A set of immune assays devoted to identifying elements of innate and specific immune response at different times post inoculation and correlate them to the presence of protection against infection will be developed and tested. The expected results will provide significant information regarding the understanding of the protective mechanism induced by other live attenuated CSFV vaccines. Amendment 1: The interaction of E2 and several host proteins have already been identified by ARS, PIADC. Recombinant CSFV harboring differnt mutations in E2 causing the disruption of the interaction with each of the host proteins will be used to evaluate the role of these E2-host protein interactions in the process of CSFV virulence in swine. These recombinant viruses will be tested at CRESA to define alterations in their virulence phenotype. Amendment 2: A trial with pregnant sows and their offspring will be performed following OIE regulations. Sows will be vaccinated with FlagT4G virus during gestation and further challenged with a virulent CSFV strain. Sows and piglets will be clinically evaluated as well as the presence of macro/ micropathological changes. Studies will be also performed to analyze the presence of challenge virus and virus-specific antibodies in different organs of the sows and piglets. These studies will evaluate the ability of the FlagT4G vaccine strain to prevent the infection of virulent field strain in pregnant sows and the consequent protection of their piglets.