UNDERSTANDING LOCAL AND SYSTEMIC PROTECTIVE RESPONSES AGAINST FOOT-AND-MOUTH DISEASE VIRUS INFECTION IN CATTLE: A GENOMICS APPROACH
Foreign Animal Disease Research
2009 Annual Report
1a.Objectives (from AD-416)
The objective of this collaborative agreement is to gain a better understanding of specific immune response to Foot-and-Mouth Disease Virus (FMDV) infection and vaccination and to identify the genetic basis of animals with high and low responder phenotypes. The objectives are: 1. to describe the early steps of the specific immune response against FMDV infection, 2. to describe the immune response elicited by inactivated FMDV vaccination, and 3. to determine the heritability of the response to FMDV vaccination in cattle populations.
1b.Approach (from AD-416)
1. The early steps of specific immune response against FMDV infection will be done through infection by aerosol inoculation delivery route and subsequent virus detection of respiratory tissues through immunostaining and real-time RT-PCR will be done. Replication sites will be correlated to anti-FMDV antibody-producing cells and studied.
2. The immune response elicited by inactivated FMDV vaccination will be studied. Cells responsible for antibody production will be determined through ELISpot assay and analyzed for protective response elicted by inactivated FMDV vaccines. These cells will genotyped with the aim of correlating host genotype with host resistance/recovery after experimental infection or induction of protection post vaccination. Results obtained from in vivo experiments will then be compared to in vitro responses.
3. The heritability of response to FMDV vaccination will be conducted studies of vaccinated bovine populations in Argentina with known pedigree. Estimates of heritability will be calculated to assess host genetic influence to FMDV vaccination response. These estimates will be used to assess merit of further efforts to identify bovine strains purported to demonstrate enhanced levels of innate resistance to FMDV. This will determine if selection for host resistance is possible and if significant gentetic differentiation is possible to identify.
INTA scientists visited ARS, PIADC and were trained in sampling of these organs and tissues in cattle and also regarding the protocols developed at PIADC for experimental infection of cattle using FMDV applied through the respiratory tract. Conditions regarding the FMDV-specific ASC ELISpot assay were set up using MAbs against FMDV and PBMC from FMDV vaccinated cattle. These experiments were performed at INTA in collaboration with the Institute of Science and Technology Cesar Milstein, depending on National Research Council of Argentina.
Sanitary services responsible for 2 dairy farms in the Province of Buenos Aires were contacted in order to use animals from these farms for the above mentioned study. Dairy farms carry out a strict genetic control of their animals, thus making possible to track parents from claves born there. Also, due to production strategy of these farms, calves are born all along the year reducing restrictions related to the breeding season. Lists of calves born to mothers belonging to these farms and from bulls used to inseminate them were generated and analyzed. Also, complete genealogic trees and HB information of these bulls within the American Dairy Bulls database were obtained and made available to other participants of this project involved in genetic characterization of the animals and sampling design.
Activities in this project were monitored through email and telephone exchange, as well as site visits to both ARS, PIADC and INTA.