Enteric Pathogens as Vaccine Vectors for Foreign Antigen Delivery

Live attenuated bacteria are attractive vaccine vectors that can elicit host immune responses to foreign antigens. Bacterial vectors may mimic natural infection and therefore interact with the mucosal, humoral, and cellular compartments of the immune system. A plethora of foreign (heterologous) antigens derived from bacterial, fungal, viral, or parasitic organisms have been expressed within bacterial vectors. Delivery of contraceptive and tumor antigens, cytokines, and adjuvants has also been explored. The result is a type of “vaccine factory” (29) in which the bacterial vector produces a foreign protein. Since bacterial vectors replicate within the host, it is hoped that they provide sustained exposure to the antigen, potentially augmenting the type and level of immune response. In addition, bacteria naturally possess immunostimulatory molecules such as lipopolysaccharide (LPS) and flagella that can stimulate immune responses (56). Internationally, there are three live bacterial vaccines commercially available and in clinical use: Salmonella enterica serovar Typhi Ty21a, Vibrio cholerae CVD 103-HgR, and Mycobacterium bovis BCG. These strains plus many other attenuated strains have been used as vectors to express heterologous antigens. Live bacterial vector vaccines have been evaluated in numerous animal and human studies, but there are currently no licensed live bacterial vector vaccines being used clinically. The most compelling rationales for the development of live bacterial vectors are the possibility of oral delivery and protection at mucosal surfaces. This review will cover attenuated bacterial enteric pathogens used as vectors to express foreign (heterologous) antigens, with emphasis on those that have reached clinical study, including Salmonella, Shigella, V. cholerae, and Listeria. This review will not cover bacterial vectors used to deliver DNA vaccines or subunit and conjugate vaccines.