Arenas Gamboa, Angela Maria (2007-05). Evaluation of microencapsulation as an improved vaccination strategy against brucellosis. Doctoral Dissertation.
Brucellosis is an important zoonotic disease of nearly worldwide distribution. Despite the availability of live vaccine strains for bovine (S19, RB51) and small ruminants (Rev 1), these vaccines have several drawbacks including residual virulence for animals and humans. Safe and efficacious immunization systems are therefore needed to overcome these disadvantages. Brucella melitensis and Brucella abortus mutants in the luxR gene were generated and investigated for theri potential use as improve vaccine candidates. Immunization with a sustained release vehicle to enhance vaccination efficacy was evaluated utilizing the live mutants in encapsulated alginate microspheres containing a non-immunogenic eggshell precursor protein of the parasite Fasciola hepatica (Vitelline protein B, VpB). BALB/c mice were immunized with either encapsulated or nonencapsulated vaccine candidates to evaluate immunogenicity, safety and protective efficacy. The results suggest that luxR mutants, are attenuated in the mouse and macrophage model and appear good and safe vaccine candidates when the immunogen is given in a microencapsulated format. We were also able to demonstrate the utility of microencapsulation in oral delivery by increasing vaccine performance of current licensed vaccine strains in a natural host, the Red Deer. Together, these results suggest that microencapsulation of live Brucella produces an enhanced delivery vaccine system against brucellosis increasing the efficacy of poorly-performing nonencapsulated vaccine candidates.