ABSTRACT
It is generally assumed that live vaccines are better than inactivated or acellular vaccines, as they are less expensive and induce a more persistent immunity. However, the microencapsulation of antigens in biodegradable polymers may turn the balance in favour of acellular vaccines. In this chapter, we describe the properties of drug-vaccine delivery systems based on the use of such polymers, and their application in the control of experimental brucellosis. We have demonstrated that micelles of major membrane antigens from Brucella ovis (HS extract) can be microencapsulated in poli-(Ɛ-caprolactone), and that this preparation (HS-PEC) induces a protective effect against a challenge against experimental brucellosis in mice and rams. The resulting microparticles had diameter sizes of less than 3 μm and contained significant amounts of the unaltered antigenic complex, which was subsequently released in pulses from the microparticles. These microparticles were injected orally or subcutaneously in BALB/c mice in order to observe the protection conferred against experimental infection with the virulent strains B. abortus 2308 or B. ovis PA. The results showed that subcutaneous administration of HS-PEC microparticles eliciting high amounts of IFN-γ and IL-2 but low quantities of IL-4, and protected mice against any of the challenge strains used. Such protection was similar to that provided by the reference live attenuated B. melitensis Rev 1 vaccine. Similarly, oral immunization was also able to protect mice challenged with B. ovis. Additional research was performed in rams, where HS-PEC was innocuous and, in contrast to Rev 1 immunized animals, did not induce antibodies against smooth lipopolysaccharide. To establish the protective value of this rough subcellular vaccine, rams were challenged with B. ovis, and found to have a similar protection level to than that conferred by Rev 1. In conclusion, protection against experimental infection in mice and rams after one single shoot, and its potential for mucosal vaccination, suggest that HS-PEC microparticles may represent a serious alternative to the conventional attenuated anti-brucellosis vaccines.
