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Title: BACTERIAL PERSISTENCE AND IMMUNITY IN GOATS VACCINATED WITH A PURE DELETION MUTANT OR THE PARENTAL 16 M STRAIN OF BRUCELLA MELITENSIS

Author
item Cheville, Norman
item Olsen, Steven
item Jensen, Allen
item Stevens, Mark
item HOUNG, H - WRAIR
item WARREN, R - WFAIR
item HADFIELD, T - WRAIR
item HOOVER, D - WRAIR

Submitted to: Infection and Immunity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/11/1995
Publication Date: N/A
Citation: N/A

Interpretive Summary: A new genetically engineered vaccine for brucellosis in humans and animals has been developed. To test the effectiveness and safety of the new vaccine, young goats were vaccinated when 8 weeks old. No clinical evidence of brucellosis was seen in any goat. Serum antibody titers peaked at 14 days and declined thereafter. The purEK mutant did not change genetically during replication in lymph nodes of goats, and may be a candidate for efficacy testing; e.g., it produced both humoral and cell-mediated immune responses, was cleared from visceral tissues, and produced no significant clinical disease or evidence of pathologic change in tissue. Brucellosis in humans and in sheep and goats is an important disease worldwide, and especially in the Middle East. Current vaccines do not provide high degrees of immunity and a more efficacious vaccine against Brucella melitensis is needed. This research was done to solve the problem of preventing brucellosis in animals and humans. The research will benefit American agriculture and the American consumer by enhancing the elimination of brucellosis from sheep and goats and from their milk, and by providing a vaccine against human brucellosis caused by Brucella melitensis. The impact of the research is not known. Benefits to the industry are not known at this time, but the research may lead to commercialization of vaccines and then to elimination of brucellosis from the animal industry.

Technical Abstract: Goats were inoculated subcutaneously with a purEK genetic deletion mutant of B. melitensis (n=6), its virulent parental strain 16M (n=6), or saline (n=6). No clinical evidence of brucellosis was seen in any goat. Serum antibody titers peaked at postinoculation day (PID) 14 and declined thereafter. Bacteria in lymph nodes that drained sites of vaccination reached peak numbers of >10(6) CFU/g in both infected groups at PID 7, and progressively declined. At necropsy, bacteria were present in mammary lymph nodes of spleen of 33% of goats given virulent 16M, but in none of goats given the purE mutant. Lymphadenitis, most severe in goats given 16M, involved depletion of lymphocytes and germinal centers, proliferation of lymphoblasts, and vasculitis with effacement of tissue architecture. The purEK mutant did not change genetically during replication in lymph nodes of goats, and can be differentiated from wild strains by hybridization, purine auxotrophy, and kanamycin resistance. The purEK mutant may be a candidate for efficacy testing; e.g., it produced both humoral and cell-mediated immune responses, was cleared from visceral tissues, and produced no significant clinical disease or evidence of pathologic change at necropsy.