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Research Project: Evaluation of Novel Foot-and-Mouth Disease Virus Vaccine Candidates with Broad Breadth of Protection - Phase II

Location: Foreign Animal Disease Research

Project Number: 3022-32000-064-015-S
Project Type: Non-Assistance Cooperative Agreement

Start Date: Aug 1, 2019
End Date: Oct 31, 2023

This research project is focused on the development of novel mosaic Foot-and-Mouth Disease Virus (FMDV) vaccine candidates for serotype O and the examination of animal immune responses. It is proposed to evaluate Mosaics for serotype O constructed by replacement of mosaic type O capsids using a type A FMDV backbone and on a live attenuated vaccine type A backbone with the capability to differentiate vaccinated from infected animals (DIVA). Development of an FMDV vaccine with broad coverage offers the possibility of manufacturing cross-protective serotype-specific vaccines, providing significant cost savings while conferring solid protection against FMDVs with distinct topotypes. In addition, ARS, PIADC is currently engaged in additional proof of concept animal experiment with the Type A mosaic immunogens and to initiate construction of mosaics for serotype O and Asia. Therefore, the main goal of this project is the development of serotype O mosaic prototype vaccines able to protect against epidemiologically relevant Type O strains. This project will generate knowledge on next generation FMDV vaccines, virus characterization and serological responses in animals, that will ultimately aid on the development of more effective prevention and control strategies against FMD. The goal of this collaborative research project is to provide animal experimental and immunological support to USDA, ARS in the characterization, evaluation of vaccine efficacy of novel type O mosaic FMDV vaccine candidates. Specific objectives include: 1. Large scale amplifies, chemically inactivate, concentrate and formulate mosaic type O FMDV vaccine/s in order to evaluate vaccine efficacy in the natural host. 2. Evaluate immune responses to mosaic versus single type O vaccine in animal: determine protective antibody and T-lymphocyte responses in cattle or swine immunized with single type O or with O Mosaic vaccine and with heterologous challenge. 3. Continue to build technical capacity to individuals that could expand their expertise on foreign animal diseases, and potentially transition to the National Bio and Agro-Defense Facility.

The Kansas State University (KSU) will provide ARS, PIADC support in the characterization and in vivo evaluation of novel FMDV vaccine candidtes. Activities will include: 1. Support to develop recombinant type A mosaic 2.1/2.2 mosaic and A24Cru vaccines and evaluation of their ability to protect against clinical disease in cattle challenged with heterologous FMDV strain, following according to the OIE manual. 2. Support in animal experiment designs to test vaccine efficacy which will include collection of appropriate samples to assess if novel vaccines prevent clinical FMD against heterologous chalenge. Determine the cellular immune response, specifically induction of cytotoxic T lymphocytes (CTL) that can kill virus-infected cells in a FMDV specific manner.