CHARACTERIZATION OF BRUCELLOSIS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Brucellosis is a chronic granulomatous infection caused by several subtypes of the intracellular bacteria Brucella. There are less than 100 cases/year of natural brucellosis in USA, which occur predominantly in California and Texas; however, due to the possibility of airborne transmission of this pathogen, Brucella is considered a potential biologic weapon (NIAID category B agent). A human vaccine has not been developed for brucellosis, and some of the successful live-attenuated vaccines (LAV) used in animals still retain pathogenicity for humans. A major difficulty affecting the development of a vaccine against human brucellosis is the absence of well-established immune correlates of protection. Pathogenicity varies among Brucella species in all mammalian species evaluated. The mouse and guinea pig model of human vaccine development have the disadvantage of using inbred strains and consequent limited generalization of the results, and low availability of reagents for a thorough characterization of the immune response to the vaccines, respectively. Nonhuman primates (NHP) are the preferred animal models for pre-clinical research because they approximate humans in physiology and genetics more closely than any other animal. NHP are susceptible to infection with virulent or attenuated strains of Brucella organisms, and recent studies have shown that rhesus macaques infected with B. melitensis 16 M develop pathologic changes similar to the ones observed in human brucellosis. The immediate goal of this project is to define the rhesus macaque model for brucellosis and to identify potential immune markers of disease progression and protection.