Selective delivery of antigens by recombinant bacteria

The means to attenuate Salmonella and to endow such avirulent strains with the ability to express colonization and virulence antigens from other pathogens has achieved considerable progress during the past several years. One can therefore begin to design and construct strains with specificity to a given animal host and to express in a defined way specific colonization and virulence antigens in a manner to stimulate long-lasting immunity to the Salmonella and to the pathogen supplying the genetic information for the colonization and virulence antigens. Since most pathogens colonize on or invade through mucosal surfaces, the use of recombinant bivalent Salmonella vaccine strains to stimulate a mucosal immune response would induce the development of a first line of defense against a diversity of pathogens. Mucosal immunity should therefore reduce contagious spread of many pathogens since the dose to overcome the mucosal immune barrier would be increased to result in a diminished likelihood of infection. The fact that the recombinant Salmonella vaccine strains also induce humoral and cellular immune responses justifies their use for induction of long-lasting immunity. Although considerable progress has been made in targeting antigens to the GALT by use of avirulent Salmonella, a similar strategy for delivery of antigens to the BALT has yet to be discovered and developed. In addition to constituting a system for induction of immunity against a diversity of pathogens, the recombinant avirulent Salmonella system should provide a means to explore parameters of the mucosal immune response. This would include investigation of the location and duration of memory, the age dependence of induction of mucosal immunity, and the means for the possible induction of oral tolerance with regard to either the mucosal or humoral response to an antigen expressed by the recombinant Salmonella. It is also possible to contemplate using the avirulent Salmonella to target expression of various modulators of the immune system such as interleukin-2 and interferon-gamma to the GALT and thus further enhance the immune response. Lastly, one can introduce into avirulent Salmonella strains genes for putative colonization antigens in order to investigate whether induction of an immune response against the putative colonization antigen does or does not interfere with infection. This system, therefore, permits another means to analyze the relative importance of various bacterial surface attributes in conferring pathogenicity to the microbe.