Immunomodulation using genetically engineered bacteria for type III-mediated delivery of heterologous antigens and cytokines: potential application in vaccine and therapeutical developments.

The rational design of new approaches aiming to improve antigen or drug delivery remains a major challenge in numerous vaccine and therapeutical strategies. Studies on genetically engineered bacteria have led to significant progress in the delivery of heterologous proteins. Yet, the efficiency of such recombinant bacteria relies particularly on their ability to deliver sufficient amount of the drug to intended cell tissues. Gram-negative bacteria like Salmonella, Shigella, Yersinia and Pseudomonas have evolved powerful secretion machinery called type III secretion system (T3SS) that is used to optimize their virulence effect by delivering bacterial effectors to the membrane or into the host cell cytoplasm. This review highlights recent studies unraveling whether T3SS of attenuated bacteria could be an efficient route for delivery of vaccine antigens or bioactive proteins such as cytokines for immunomodulation that could find a broad range of application purposes. These current experimental investigations can be considered proofs of concept that need to be translated readily to effective vaccines and therapeutics in humans.