Autodisplay: development of an efficacious system for surface display of antigenic determinants in Salmonella vaccine strains.
To optimize antigen delivery by Salmonella vaccine strains, a system for surface display of antigenic determinants was established by using the autotransporter secretion pathway of gram-negative bacteria. A modular system for surface display allowed effective targeting of heterologous antigens or fragments thereof to the bacterial surface by the autotransporter domain of AIDA-I, the Escherichia coli adhesin involved in diffuse adherence. A major histocompatibility complex class II-restricted epitope, comprising amino acids 74 to 86 of the Yersinia enterocolitica heat shock protein Hsp60 (Hsp60(74-86)), was fused to the AIDA-I autotransporter domain, and the resulting fusion protein was expressed at high levels on the cell surface of E. coli and Salmonella enterica serovar Typhimurium. Colonization studies in mice vaccinated with Salmonella strains expressing AIDA-I fusion proteins demonstrated high genetic stability of the generated vaccine strain in vivo. Furthermore, a pronounced T-cell response against Yersinia Hsp60(74-86) was induced in mice vaccinated with a Salmonella vaccine strain expressing the Hsp60(74-86)-AIDA-I fusion protein. This was shown by monitoring Yersinia Hsp60-stimulated IFN-gamma secretion and proliferation of splenic T cells isolated from vaccinated mice. These results demonstrate that the surface display of antigenic determinants by the autotransporter pathway deserves special attention regarding the application in live attenuated Salmonella vaccine strains.
Kramer
Uwe
U
Institut für Medizinische Mikrobiologie und Krankenhaushygiene, Universität Tübingen, D-72076 Tübingen, Germany.
Rizos
Konstantin
K
Apfel
Heiko
H
Autenrieth
Ingo B
IB
Lattemann
Claus T
CT
D018830:Adhesins, Escherichia coli / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018834:Chaperonin 60 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005822:Genetic Vectors; D006090:Gram-Negative Bacteria / Q000235:genetics / Q000276:immunology; D007114:Immunization; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011993:Recombinant Fusion Proteins / Q000276:immunology; D022562:Salmonella Vaccines / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology
C075559:AIDA-I protein, E coli; D018830:Adhesins, Escherichia coli; D000942:Antigens, Bacterial; D000954:Antigens, Surface; D018834:Chaperonin 60; D011993:Recombinant Fusion Proteins; D022562:Salmonella Vaccines; D007371:Interferon-gamma