Location: Foreign Animal Disease Research2012 Annual Report
1a. Objectives (from AD-416):
The objective of this collaborative research project is to accelerate the development of vaccine technology for two critical cattle diseases; foot-and-mouth disease (FMD) and east coast fever (ECF), impacting smallholder farmers in sub-Saharan Africa. We will utilize vaccine development technologies which assess breed specific host responses to pathogens utilizing existing genome sequences for two targeted pathogens and the genome sequence of the host species, Bos taurus. ARS, PIADC will lead the effort to analyze the immune response to FMDV infection in cattle as well as the analysis of FMD vaccine performance.
1b. Approach (from AD-416):
The bovine immune response to FMDV infection will be assessed through bioinformatics, high-throughput sequencing, peptide synthesis, proteomics and ultimately the major histocompatibility complex (MHC) tetramer technology or "tetramers". ARS will expand the present collaboration with the University of Vermont to achieve a more technically sophisticated and informative analysis of the immune response of cattle to FMDV infection and to vaccination with virus vectored FMD vaccines. This is made possible by utilizing the genetically defined animals from the University of Vermont's herds of Holstein cattle, or from the University of Vermont Dairy Center of Excellence cooperator herds.
3. Progress Report:
The major histocompatibility complex (MHC) class I and class II genes are critical in the T-cell mediated immune response to intracellular pathogens including viruses (class I MHC) and the adaptive immune response mediated through antigen presenting cells (class II MHC). The bovine class I and class II gene structure and sequence diversity are poorly understood, representing an obstacle in our understanding of antigen specific responses to pathogens and vaccine candidates. The goal of this collaborative agreement is to determine allele diversity and frequency of the MHC class II genes in a herd of pure-bred registered Holstein dairy cattle (University of Vermont Research Herd). This will be accomplished by tissue typing the MHC of Holstein dairy cattle and developing tools to study the T cell response to Foot and Mouth Disease (FMD) virus. Specifically by quantifying the extent of MHC class II diversity we will establish the potential for use of tetramer technology to study the immune response to FMD virus and a FMD vaccine candidate currently under development by USDA-ARS. In addition, we will select representative MHC types to evaluate the Holstein immune response to an adenovirus vectored FMD vaccine using tetramer technology. During FY 2012 we conducted the analysis of bovine leukocyte antigens (BoLA) Class II expression in 84 Holstein cattle from Nordic Farm, a UVM Dairy Center of Excellence Research herd, which has identified 4 dominant BoLA class II haplotypes which are present in 92% of animals tested. Further patterns of allelic expression are being identified in individual animals contributing to our understanding of class II gene expression and the potential relationship between class I and class II expression. Methods for Class II BoLA-DRB3 allelic typing have been transferred from the lab in Washington State University to USDA-PIADC. No publications have been prepared during this reporting period.