ABSTRACT

Brucellosis causes substantial morbidity in humans and exacts a considerable economic toll on both the health care and livestock industries. Recently, the long-recognized potential use of Brucella as a bioweapon coupled with growing concern over bioterrorism has led to its classification by the United States Centers for Disease Control as a Category B biological threat agent. Elimination of brucellosis in food animals is the preferred method to prevent naturally acquired disease in humans, but this approach would not protect against illicit use of the organism as a bioweapon. Development of a human vaccine would be valuable both as a biodefense strategy and as an interim solution for prevention of naturally acquired human disease in situations where economic or sociological factors prevent application of an effective animal disease control program. Indeed, the need to protect occupationally high-risk workers and other susceptible populations has led to a number of efforts at human vaccine development. These efforts have met with variable success, but none has resulted in a well-accepted product. The recent explosion in genetic information on Brucella as a result of complete sequencing of the B. suis, B. melitensis and B. abortus genomes may provide an opportunity to make safe and effective vaccines for humans and improve on those available for animals. Novel molecular based vaccine strategies, which may include DNA vaccination, new adjuvants and selection of immunogens based on genomic and proteomic screening methods may lead to development of subunit vaccines, with potential safety advantages over living organisms. In the near future, however, live attenuated vaccines will be the gold standard for efficacy.

In this chapter, we will focus on live, attenuated human vaccines. We will review previous human studies and examine aspects of interactions between Brucella and its host that are relevant for development of appropriate animal models for testing and for vaccine design. We will then discuss work in nonhuman 370primates and summarize results from our own program, which has established mucosal challenge models of infection to assess vaccine efficacy and uses molecular methods to develop live, attenuated vaccines. Finally, we will survey recent work that identifies other interesting targets for vaccine development.