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There is a need to develop vaccines with the potential for global use against bacterial infectious diseases. These should be inexpensive to produce, stable in the absence of refrigeration, safe and efficacious, and able to be given orally or intranasally rather than by injection. Here, I will focus on efforts to develop live attenuated bacterial vaccines and the use of recombinant attenuated bacteria to induce protective immunity against heterologous bacterial pathogens. I will not discuss bacterial vaccine vectors expressing viral, parasite, or fungal antigens, since lack of posttranslational modification and improper folding generally lead to induction of immune responses that are not protective, although induction of cell-mediated immunity can often be protective. Also omitted will be a discussion of the use of attenuated bacterial vaccine vectors for the delivery of DNA vaccines, wherein problems of processing of viral, parasite, and fungal antigens in bacteria are rectified by the synthesis and modification of these antigens within the eukaryotic cell. Lastly, although I acknowledge their value, especially in the developed world, I will not dwell on progress in the development of subunit and conjugate vaccines. Studies of such vaccines, however, often provide valuable information on identification and characterization of protective antigens that can be expressed in live recombinant attenuated bacterial vaccines of the kind I consider below.

Bacterial infectious disease control by vaccine development