Salmonella as Live Carrier of Antigens in Vaccine Development

Abstract

Attenuated Salmonella strains have been extensively used as live carriers of heterologous antigens. In animal models they elicit strong mucosal and systemic immune responses to passenger antigens of a broad variety of pathogens. Salmonella has several theoretical advantages over other vaccine vector systems. Among them, especially attractive is the bacterial ability to interact with mucosal and systemic compartments of the immune system and deliver passenger antigens directly to antigen presenting cells (APC) when administered by the oral route. However, despite the promising results in animal models, clinical trails have been disappointing and more research is needed in order to understand the protective immunity mechanisms and solve the main drawbacks of vaccine design. Herein, we summarize the accumulated experience using Salmonella as live carrier emphasizing the role of passenger antigen localization into different bacterial compartments. This is an important factor determining the type and quality of the host immune response. The evidence suggests that antigens located on the bacterial surface induce higher antibody responses whereas those located in the cytoplasm elicit better cellular immunity. In order to display recombinant antigens on the bacterial surface we have used outer membrane (OMPs) or autotransporter proteins. Mice immunized with Salmonella strains expressing the main B cell epitope from the Plasmodium falciparum circumspozoite protein, presented better antibodies response when placed on the bacterial surface as a fusion proteins with OMPs or autotransporters, than the whole recombinant protein located in the bacterial cytoplasm.