Chimeric Vaccines based on Type 1 Fimbriae

An attractive way of engineering vaccines is to fuse immunologically relevant sectors of an important protein antigen into a naturally occurring bacterial surface protein such as fimbriae.
We use structural elements from a bacterial organelle system, fimbriae, for this purpose. Fimbriae, which are bacterial adhesins that enable bacteria to target to and to colonize specific host tissues, are long tread-like surface organelles, found in up to about 500 copies per cell. We have used elements from the type 1 fimbrial system for integration of heterolo-gous sequences, representing the preS2 sector of the hepatitis B surface antigen and an epitope from cholera toxin, and show them to be authenti-cally exposed on the surface of the fimbriae, which in turn are present on the surface of bacterial hosts. Immunization of rabbits with purified chimeric fimbriae resulted in serum which specifically recognized the foreign epitope. Several other important epitopes have been integrated. We are currently developing live vaccine strains based on harmless host bacteria. These are engineered to express chimeric fimbriae. The technology should result in cheap and efficient vaccines against a spectrum of diseases.