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Research Project: Understanding Cross-Reactive Responses Between Heterologous Foot-and-Mouth Disease Virus Strains in the Bovine Model

Location: Foreign Animal Disease Research

Project Number: 3022-32000-064-007-S
Project Type: Non-Assistance Cooperative Agreement

Start Date: Sep 1, 2018
End Date: Aug 31, 2023

A reoccurrence of Foot-and-Mouth Disease Virus (FMDV) in Ecuador in 2009 showed that animals vaccinated with O1/Campus vaccine strain were not protected against challenge with O Ecuador field isolates. Animals vaccinated with a single dose of bivalent formulation of O1/Campos and A24/Cruzeiro strains only achieved 50% protection. Two doses of the commercial bivalent vaccine resulted in almost complete protection. This research project seeks to perform a rational study of the heterologous protection between FMDV strains within the same serotype from the host and determine the antigenic determinants. Amendment I: Will produce and test, following the same experimental design as described above, for two additional sets of serum samples obtained after immunization with monovalent FMD vaccines from the A24/Cruzeiro and C3/Indaial strains.

A rational study of the heterologous protection between Foot-and-Mouth Disease Virus (FMDV) strains within the same serotype will be conducted using a well-characterized field-derived model between two O serotype strains: the O1/Campos strain -commonly included in commercial vaccines- and a virus isolate (O Ecuador) obtained during the 2009-2011 FMDV outbreaks in South America. We will generate six experimental groups of cattle using two oil FMD vaccines: a high payload C3 Indial vaccine, a high payload A24 vaccine and a trivalent vaccine carrying the approximately the same amount of viral antigen but comprising the A24/Cruzeiro and C3/Indaial strains, as well. Two groups will receive a single dose of each vaccine. The other two will be revaccinated with the same formulation at 30 days post-primary immunization. In parallel, we will use the infectious-clone technology available at ARS, PIADC to generate a range of recombinant viruses carrying different antigenic sites from the O Ecuador isolates into the O1/Campos structure. Host immune responses induced in each experimental group at different times post-vaccination will be studied. A set of infectious FMDV chimeras will be used to analyze the presence of cross-neutralizing antibodies by virus-neutralizing test (VNT). These recombinant FMDVs, as well as from the O1/Campos and O Ecuador native strains will be used for different immunologic assays developed at INTA to characterize FMDV-specific humoral and cellular responses as well as cross-reactive memory responses, both for B- and T-lymphocytes. We expect to identify immunological parameters that may help to establish potential cross-protection among different FMDV strains, as well as to characterize structural features within the virus capsid that may contribute to the rational design of recombinant FMDVs with broader antigenic span.