Brucellosis is a chronic disease which has tremendous importance worldwide for both human and animal health. In animals, brucellosis results in abortion and infertility, while in humans the disease is known as undulant fever. Human disease results from exposure to infected animals or contaminated animal products. For this reason, the control of brucellosis in humans and animals, particularly food animals, is intimately associated. Live attenuated vaccines have proven to be effective for controlling brucellosis in cattle, goats and swine, but these vaccines are unsuitable for use in humans. Although the live vaccines induce protective immunity in a large percentage of animals, the nature of the protective immune response in not known. Both cell-mediated and humoral immunity are believed to be important. The primary objective of the studies outlined in this proposal is to define the role of individual antigens of Brucella abortus in the protective immune response. Past attempts using native B. abortus antigens have been complicated by consistent contamination with the immunodominant LPS of B.abortus. In the studies proposed here, recombinant B. abortus antigens produced in T. coli which are recognized by sera from infected animals in immunoassay, will be used. The ability of recombinant E. coli fractions to produce an antibody response, cell-mediated immunity, and protection against challenge with B. abortus, will be examined in BALB/c mice. The identity of the native B. abortus antigens represented by the recombinant antigens will also be determined. The genetic sequences coding for the recombinant antigens will be used to construct recombinant vectors which will be introduced into an attenuated strain of Salmonella typhimurium. BALB/c will then be immunized orally with live, attenuated recombinant S. typhimurium clones and the ability of these clones to induce antibody production, cell-mediated immunity and protection against challenge with B. abortus assessed. Results of these studies will not only provide critical data for evaluating the potential of subunit or live recombinant vaccines for human and animal brucellosis, but they may also provide information relevant to the nature of facultative intracellular parasitism, of which brucellosis is a prime example.
