Abstract: No vaccines are currently licensed to prevent human brucellosis and existing vaccines for livestock are not entirely efficacious. In humans and other animals, Brucella can cause a lifelong infection. However, mechanisms underlying the ability of Brucella to subvert adaptive immunity remain unclear. In this proposal we show that vaccine elicited antibodies alter host metabolism to protect the host against Brucella to some degree. Therefore, in Specific Aim #1 of this proposal we will determine how vaccine-elicited IgM and class switched antibodies alter tissue metabolism to restrict Brucella infection. We also found that Brucella encodes virulence factors that mediate evasion of humoral immunity. Therefore, in Specific Aim #2 of this proposal we will identify mechanisms by which Brucella subverts antibody mediated immunity. Collectively, our results will enhance our understanding of how current vaccines protect the host, and how Brucella is able to subvert adaptive immunity, and thus could improve the rational design of highly effective vaccines for Brucella.