Recombinant attenuated bacteria for the delivery of subunit vaccines

• Published in: Vaccine 2001-03, Vol.19 (17), p.2621-2628
• Main Authors: Gentschev, Ivaylo, Dietrich, Guido, Spreng, Simone, Kolb-Mäurer, Annette, Brinkmann, Volker, Grode, Leander, Hess, Jürgen, Kaufmann, Stefan H.E., Goebel, Werner
• Format: Article
• Language: English
• Subjects: Animals; Antigens - biosynthesis; Antigens - genetics; Applied microbiology; Attenuated bacterium; Bacteria - genetics; Bacteria - immunology; Bacteria - ultrastructure; Biological and medical sciences; DNA vaccine delivery; Drug Delivery Systems; Escherichia coli - genetics; Escherichia coli - immunology; Escherichia coli hemolysin secretion system; Fundamental and applied biological sciences. Psychology; Genetic Vectors; Hemolysin Proteins - administration & dosage; Listeria; Listeria monocytogenes - genetics; Listeria monocytogenes - immunology; Listeria monocytogenes - ultrastructure; Mice; Mice, Inbred BALB C; Microbiology; Microscopy, Electron; Plasmids - genetics; Salmonella; Salmonella typhimurium - genetics; Salmonella typhimurium - immunology; Salmonella typhimurium - ultrastructure; Vaccine; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, Attenuated - administration & dosage; Vaccines, Attenuated - genetics; Vaccines, DNA - administration & dosage; Vaccines, DNA - genetics; Vaccines, Subunit - administration & dosage; Vaccines, Subunit - genetics
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/S0264-410X(00)00502-8

Using attenuated intracellular bacteria as carriers, we have developed two different approaches for the delivery of subunit vaccines encoding heterologous antigens. The first system is based on the direct secretion of the heterologous antigens in Gram-negative bacteria via the hemolysin secretion system of Escherichia coli into either phagosome or cytosol of infected cells. The second approach is based on the transport of eukaryotic antigen expression vectors by intracellular bacteria like Listeria and Salmonella into the host cell and here, preferably, into the cytosolic compartment. After release of the plasmid DNA from the bacteria, the plasmid-encoded antigens can be expressed directly by the host cell. Finally, we combined both types of subunit vaccines in one live vector — we equipped Salmonella strains with a phagosomal escape function by utilization of the hemolysin secretion system and used this recombinant vaccine strain for the delivery of a eukaryotic antigen expression vector into the cytosol of macrophages.