Autodisplay:: Development of an efficacious system for surface display of antigenic determinants in Salmonella vaccine strains

被引:33
作者
Kramer, U
Rizos, K
Apfel, H
Autenrieth, IB
Lattemann, CT
机构
[1] Univ Tubingen, Inst Med Mikrobiol, D-72076 Tubingen, Germany
[2] Univ Tubingen, Krankenhaushyg, D-72076 Tubingen, Germany
[3] CREATOGEN AG, D-86156 Augsburg, Germany
关键词
D O I
10.1128/IAI.71.4.1944-1952.2003
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 (Hsp6074-ab), 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.
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页码:1944 / 1952
页数:9
相关论文
共 46 条
[11]   Can a 'flawless' live vector vaccine strain be engineered? [J].
Galen, JE ;
Levine, MM .
TRENDS IN MICROBIOLOGY, 2001, 9 (08) :372-376
[12]   Delivery of protein antigens and DNA by virulence-attenuated strains of Salmonella typhimurium and Listeria monocytogenes [J].
Gentschev, I ;
Dietrich, G ;
Spreng, S ;
Kolb-Mäurer, A ;
Daniels, J ;
Hess, J ;
Kaufmann, SHE ;
Goebel, W .
JOURNAL OF BIOTECHNOLOGY, 2000, 83 (1-2) :19-26
[13]   THE BIOCHEMISTRY AND CELL BIOLOGY OF ANTIGEN PROCESSING AND PRESENTATION [J].
GERMAIN, RN ;
MARGULIES, DH .
ANNUAL REVIEW OF IMMUNOLOGY, 1993, 11 :403-450
[14]   CHLAMYDIA-TRACHOMATIS MAJOR OUTER-MEMBRANE PROTEIN EPITOPES EXPRESSED AS FUSIONS WITH LAMB IN AN ATTENUATED AROA STRAIN OF SALMONELLA-TYPHIMURIUM - THEIR APPLICATION AS POTENTIAL IMMUNOGENS [J].
HAYES, LJ ;
CONLAN, JW ;
EVERSON, JS ;
WARD, ME ;
CLARKE, IN .
JOURNAL OF GENERAL MICROBIOLOGY, 1991, 137 :1557-1564
[15]   Superior efficacy of secreted over somatic antigen display in recombinant Salmonella vaccine induced protection against listeriosis [J].
Hess, J ;
Gentschev, I ;
Miko, D ;
Welzel, M ;
Ladel, C ;
Goebel, W ;
Kaufmann, SHE .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (04) :1458-1463
[16]  
Hess J, 1996, J IMMUNOL, V156, P3321
[17]   MACROPHAGE-INDUCIBLE EXPRESSION OF A MODEL ANTIGEN IN SALMONELLA-TYPHIMURIUM ENHANCES IMMUNOGENICITY [J].
HOHMANN, EL ;
OLETTA, CA ;
LOOMIS, WP ;
MILLER, SI .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (07) :2904-2908
[18]   Rational live oral carrier vaccine design by mutating virulence-associated genes of Yersinia enterocolitica [J].
Igwe, EI ;
Rüssmann, H ;
Roggenkamp, A ;
Noll, A ;
Autenrieth, IB ;
Heesemann, J .
INFECTION AND IMMUNITY, 1999, 67 (10) :5500-5507
[19]   INFLUENCE OF AMINO-ACIDS OF A CARRIER PROTEIN FLANKING AN INSERTED T-CELL DETERMINANT ON T-CELL STIMULATION [J].
JANSSEN, R ;
WAUBEN, M ;
VANDERZEE, R ;
DEGAST, M ;
TOMMASSEN, J .
INTERNATIONAL IMMUNOLOGY, 1994, 6 (08) :1187-1193
[20]  
Janssen R, 1994, Int Rev Immunol, V11, P113, DOI 10.3109/08830189409061719