© INSTITUT PASTEUR/ELSEVIER Res. Microbiol. Paris 1990 1990, 141, 745-746

I N T R O D U C T I O N

Two years after the Albany meeting on "Vector-based vaccines" where Enzo Paoletti gathered scientists working on both viral and bacterial systems, it seemed to us that a meeting completely devoted to bacterial vectors and vehicles was justified.

Research on the use of recombinant bacteria for oral immunization is expanding rapidly° The idea consists of using an attenuated mutant of a virulent bacterium to deliver heterologous antigens to the immune system in such a way that they trigger protective responses not only against the bacterium but also against the other patho- gens from which the foreign antigens are derived. Such recombinant strains are usually composed of a genetically attenuated mutant o f a pathogenic bacterium (the vehicle) and a genetic construction (the vector) devised to obtain an adequate expression of critical antigens from one or severai other pathogens (the passenger antigens). It is expected that judicious choice of the vehicle, the vectors and the antigens will lead to the desired protective immunity.

,, This volume originates from the communications presented at the workshop on Oral immunization using recombinant bacteria" held in Munich, FRG, June 6 to 8,

1990. It gives an up-to-date view of current work in the fields discussed at this meet- ing. The four sections of the volume reflect four areas in which important efforts and progress are being made.

Immunity and infection. - - The more we know on the nature of the immune response to pathogens and on the pathways of infection, the better our capacity to devise strains suitable for oral immunization. For example, certain bacteria are capable of eliciting cytotoxic T-lymphocyte responses which might be important and some- times critical for vaccine use. This first section partially covers these subjects and serves as an introduction to the workshop.

Salmonella. - - Most work done so far involved the use of S. typhimurium or S. en- teritidis in small animal models, or S. typhi in man. These bacteria represent vehi- cles which have been most thoroughly studied. Work on the attenuation and immunogenicity of these bacteria as well as various examples of their use for the delivery of foreign antigens are described in some detail in the second section.

Other bacteria. - - The molecular pathogenesis of some other bacteria which are potentially useful for oral immunization is intensively investigated and leads to the characterization of possibly useful attenuated mutants. These bacteria include Es- cherichia, Mycobacteria, Shigella, Vibrio cholerae, Yersinia, etc. This section presents some of the most recent results with several of these other potential vehicles.

Expression systems. - - The role of the mode of expression of the foreign anti- gens is also being explored. The localization of the antigen within the bacterial cell as well as the timing of expression are among the parameters which appear to in- fluence the immune response. This last section presents a number of expression sys- tems, some of which are original attempts at optimizing the conditions of delivery of the foreign antigens or parts thereof.

Many scientific questions remain open. What are the best suited vehicles and vec- tors for a given antigen ? It is possible to repeatedly use the same vehicle strain in

746 I N T R O D U C T I O N

the same subject ? Can we rely on the expression of critical fragments o f amigens to induce a protective response 7... Due to the rapid pace o f research in the field, we should have at least partial answers to these and other questions in the near future.

Provided all scientific difficulties have been resolved for a given vehicle/vec- tor/antigen combination, the question arises as to the. a.~ceptability o f such vaccines by regulatory authorities. In that respect, it should be noted that gowth and dissemi- nation o f live bacterial vehicles can be controlled by a large number o f antibiotics. This may be an important advantage over viral vectors.

Florian Sch6del Maurice llofnung Max Planck Institute fiir Biochemie Institut Pasteur

Marti~sried bei Miinchen Paris

We would like to thank the Waiter Schulz and the Carl Friedrich yon Siemens Stiftung for the gener- ous support which made this meeting possible.