Immune inductor and effector sites in the upper airways of cattle and influence of site of antigen expression on induction of mucosal immunity

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Many micro-organisms that cause disease in cattle enter the animal's body by invading the respiratory tract. A number of micro-organisms which invade cattle in this way are a significant threat to animal welfare and cause severe economic loss. Examples include the bacteria, Mycobacterium bovis, which causes bovine tuberculosis, and the virus that causes foot and mouth disease. Although vaccines to a number of such micro-organisms are available, many are only partially effective. This may be partly due to their failure to induce antibodies in respiratory secretions that prevent the micro-organisms from attaching to and colonising the cells lining the respiratory tract or from penetrating and replicating within these cells. There is therefore a clear need to develop more effective vaccines that induce protective immunity in the upper airways of cattle. There is increasing evidence that nasal delivery of vaccines is superior to vaccination at other sites in eliciting protection within the respiratory tract. However, safe and effective nasal vaccines have proved difficult to develop. The purpose of this project is to gain a more detailed understanding of the ways in which the upper airways of cattle respond to infection and mount a protective immune response. This will be achieved by studying in the laboratory the interactions of a live virus that expresses foreign genes and infects the bovine respiratory tract without causing disease, cultures of bovine airway cells and cells of the immune system that have been obtained from different regions of the upper airways of cattle. The findings from these laboratory studies will be compared with immune responses induced after nasal delivery of the viruses to calves. The information generated from this project will aid the design of effective nasal vaccines to protect cattle against a number of important infectious diseases such as foot and mouth disease and bovine tuberculosis. In addition, these studies may lead to the development of laboratory methods for testing new nasal vaccines, thereby reducing the number of animals used in research.