ABSTRACT
It is doubtful that Louis Pasteur could have anticipated the significance in 1881 that his discovery o f bacterial attenuation would have on the use o f microorganisms to protect against infectious diseases. Now, more than a century later, live attenuated bacterial vac cines have been developed that elicit sustained and protective immune responses (for a review see ref. 1). A novel application o f these vaccines has been their use as vectors to deliver foreign antigens. This type o f delivery is attractive for a number o f reasons. For example, a live replicat ing vector can express in situ both heterologous antigens and native immunomodulatory fac tors, potentially obviating the need to add an adjuvant in cases where one might ordinarily be required. Another benefit is the exploitation o f a vector’s natural route o f entry to deliver a foreign antigen. Presentation o f an antigen in this manner often mimics natural infection and would presumably result in a broader spectrum o f both mucosal and systemic immune responses. Finally, advances in molecular biology have enabled the genetic manipulation o f most bacterial vectors and provide an opportunity to deliver a wide variety o f protective immunogens.