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.