Identification of Brucella Melitensis Antigens Lymphocytes and Oral Immunization Potential of the Antigens.
Annual rept. 1 Jun 94-31 May 95,
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We have produced substantial results related to the objectives of our Department of Defense funding 1 Identified five Brucella proteins and sequenced their respective genes L71L12, LlO, uvrA, SSB, and a transporter containing an ATh binding domain - employing a rapid and dIrect technique to isolate Brucella genes from a genomic library using lymphocytes as probes and obtained two additional genes GroEL and GroES whose proteins also stimulate lymphocyte proliferation. 2 Our recently published data indicates we have successfully identified, isolated, cloned, and sequenced genes and expressed proteins that induce proliferation of lymphocytes from many Brucella immunized animals suggesting immunenodominant proteins. 3 We now have unprecedented data establishing CD8 T cells as essential to protection against B. abortus infection using MMC class II gene knockout mice. These knockout mice are profoundly deficient in CD4 T cells but rapidly clear the infection, revealing the pivotal role of CD8 T cells in protection. Our murine experiments provide the necessary foundation to explore the mechanisms of Brucella pathogenesis and in vivo protection attributable to Brucella proteins that induce T cell responses in vitro. We are positioned to apply this practical information to vaccine studies for protection against B. melitensis challenge and provide critical data necessary for a human vaccine.
- Medicine and Medical Research