Secretory delivery of recombinant proteins in attenuated Salmonella strains: potential and limitations of Type I protein transporters.
Live attenuated Salmonella strains have been extensively explored as oral delivery systems for recombinant vaccine antigens and effector proteins with immunoadjuvant and immunomodulatory potential. The feasibility of this approach was demonstrated in human vaccination trials for various antigens. However, immunization efficiencies with live vaccines are generally significantly lower compared to those monitored in parenteral immunizations with the same vaccine antigen. This is, at least partly, due to the lack of secretory expression systems, enabling large-scale extracellular delivery of vaccine and effector proteins by these strains. Because of their low complexity and the terminal location of the secretion signal in the secreted protein, Type I (ATP-binding cassette) secretion systems appear to be particularly suited for development of such recombinant extracellular expression systems. So far, the Escherichia coli hemolysin system is the only Type I secretion system, which has been adapted to recombinant protein secretion in Salmonella. However, this system has a number of disadvantages, including low secretion capacity, complex genetic regulation, and structural restriction to the secreted protein, which eventually hinder high-level in vivo delivery of recombinant vaccines and effector proteins. Thus, the development of more efficient recombinant protein secretion systems, based on Type I exporters can help to improve efficacies of live recombinant Salmonella vaccines. Type I secretion systems, mediating secretion of bacterial surface layer proteins, such as RsaA in Caulobacter crescentus, are discussed as promising candidates for improved secretory delivery systems.
Hahn
Heinz P
HP
Chirurgische Universitätsklinik, Chirurgische Forschung, i. Br., Freiburg, Germany. hanh@ch11.ukl.uni-freiburg.de
von Specht
Bernd Ulrich
BU
D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins; D001428:Bacterial Vaccines / Q000235:genetics / Q000378:metabolism; D006460:Hemolysin Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins / Q000378:metabolism*; D012475:Salmonella / Q000235:genetics*; D014613:Vaccines, Attenuated / Q000235:genetics / Q000378:metabolism
D018528:ATP-Binding Cassette Transporters; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D006460:Hemolysin Proteins; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; C055764:S-layer proteins; D014613:Vaccines, Attenuated