Decoration of Outer Membrane Vesicles with Multiple Antigens by Using an Autotransporter Approach

被引:93
作者
Daleke-Schermerhorn, Maria H. [1 ,2 ]
Felix, Tristan [3 ,4 ]
Soprova, Zora [1 ]
ten Hagen-Jongman, Corinne M. [1 ,2 ]
Vikstrom, David [5 ,6 ]
Majlessi, Laleh [3 ,4 ]
Beskers, Joep [1 ]
Follmann, Frank [7 ]
de Punder, Karin [8 ]
van der Wel, Nicole N. [8 ]
Baumgarten, Thomas [5 ]
Pham, Thang V. [9 ]
Piersma, Sander R. [9 ]
Jimenez, Connie R. [9 ]
van Ulsen, Peter [1 ]
de Gier, Jan-Willem [5 ]
Leclerc, Claude [3 ,4 ]
Jong, Wouter S. P. [1 ,2 ]
Luirink, Joen [1 ,2 ]
机构
[1] Vrije Univ Amsterdam, Fac Earth & Life Sci, Dept Mol Cell Biol, Sect Mol Microbiol, Amsterdam, Netherlands
[2] Abera Biosci AB, Stockholm, Sweden
[3] Inst Pasteur, Unite Regulat Immunitaire & Vaccinol, Paris, France
[4] INSERM, U1041, Paris, France
[5] Stockholm Univ, Dept Biochem & Biophys, Ctr Biomembrane Res, S-10691 Stockholm, Sweden
[6] Xbrane Biosci AB, Stockholm, Sweden
[7] Statens Serum Inst, Dept Infect Dis Immunol, DK-2300 Copenhagen, Denmark
[8] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Amsterdam, Netherlands
[9] Vrije Univ Amsterdam, Med Ctr, OncoProte Lab, Dept Med Oncol, Amsterdam, Netherlands
关键词
GRAM-NEGATIVE BACTERIA; PATHOGENIC ESCHERICHIA-COLI; SALMONELLA-TYPHIMURIUM; MONOCLONAL-ANTIBODIES; CHLAMYDIA-TRACHOMATIS; HEMOGLOBIN PROTEASE; MASS-SPECTROMETRY; CRYSTAL-STRUCTURE; PROTEINS; VACCINE;
D O I
10.1128/AEM.01941-14
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Outer membrane vesicles (OMVs) are spherical nanoparticles that naturally shed from Gram-negative bacteria. They are rich in immunostimulatory proteins and lipopolysaccharide but do not replicate, which increases their safety profile and renders them attractive vaccine vectors. By packaging foreign polypeptides in OMVs, specific immune responses can be raised toward heterologous antigens in the context of an intrinsic adjuvant. Antigens exposed at the vesicle surface have been suggested to elicit protection superior to that from antigens concealed inside OMVs, but hitherto robust methods for targeting heterologous proteins to the OMV surface have been lacking. We have exploited our previously developed hemoglobin protease (Hbp) autotransporter platform for display of heterologous polypeptides at the OMV surface. One, two, or three of the Mycobacterium tuberculosis antigens ESAT6, Ag85B, and Rv2660c were targeted to the surface of Escherichia coli OMVs upon fusion to Hbp. Furthermore, a hypervesiculating Delta tolR Delta tolA derivative of attenuated Salmonella enterica serovar Typhimurium SL3261 was generated, enabling efficient release and purification of OMVs decorated with multiple heterologous antigens, exemplified by the M. tuberculosis antigens and epitopes from Chlamydia trachomatis major outer membrane protein (MOMP). Also, we showed that delivery of Salmonella OMVs displaying Ag85B to antigen-presenting cells in vitro results in processing and presentation of an epitope that is functionally recognized by Ag85B-specific T cell hybridomas. In conclusion, the Hbp platform mediates efficient display of (multiple) heterologous antigens, individually or combined within one molecule, at the surface of OMVs. Detection of antigen-specific immune responses upon vesicle-mediated delivery demonstrated the potential of our system for vaccine development.
引用
收藏
页码:5854 / 5865
页数:12
相关论文
共 65 条
[1]   A multistage tuberculosis vaccine that confers efficient protection before and after exposure [J].
Aagaard, Claus ;
Hoang, Truc ;
Dietrich, Jes ;
Cardona, Pere-Joan ;
Izzo, Angelo ;
Dolganov, Gregory ;
Schoolnik, Gary K. ;
Cassidy, Joseph P. ;
Billeskov, Rolf ;
Andersen, Peter .
NATURE MEDICINE, 2011, 17 (02) :189-U224
[2]   Membrane vesicles are immunogenic facsimiles of Salmonella typhimurium that potently activate dendritic cells, prime B and T cell responses, and stimulate protective immunity in vivo [J].
Alaniz, Robert C. ;
Deatherage, Brooke L. ;
Lara, Jimmie C. ;
Cookson, Brad T. .
JOURNAL OF IMMUNOLOGY, 2007, 179 (11) :7692-7701
[3]  
ANDERSEN P, 1995, J IMMUNOL, V154, P3359
[4]  
Baba Tomoya, 2008, V416, P171, DOI 10.1007/978-1-59745-321-9_11
[5]   MAPPING ANTIGENIC DOMAINS EXPRESSED BY CHLAMYDIA-TRACHOMATIS MAJOR OUTER-MEMBRANE PROTEIN GENES [J].
BAEHR, W ;
ZHANG, YX ;
JOSEPH, T ;
SU, H ;
NANO, FE ;
EVERETT, KDE ;
CALDWELL, HD .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (11) :4000-4004
[6]   Immunity to Intracellular Salmonella Depends on Surface-associated Antigens [J].
Barat, Somedutta ;
Willer, Yvonne ;
Rizos, Konstantin ;
Claudi, Beatrice ;
Maze, Alain ;
Schemmer, Anne K. ;
Kirchhoff, Dennis ;
Schmidt, Alexander ;
Burton, Neil ;
Bumann, Dirk .
PLOS PATHOGENS, 2012, 8 (10)
[7]   Alkanols and chlorophenols cause different physiological adaptive responses on the level of cell surface properties and membrane vesicle formation in Pseudomonas putida DOT-T1E [J].
Baumgarten, Thomas ;
Vazquez, Jose ;
Bastisch, Christian ;
Veron, Wilfried ;
Feuilloley, Marc G. J. ;
Nietzsche, Sandor ;
Wick, Lukas Y. ;
Heipieper, Hermann J. .
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY, 2012, 93 (02) :837-845
[8]   Escherichia coli tol-pal mutants form outer membrane vesicles [J].
Bernadac, A ;
Gavioli, M ;
Lazzaroni, JC ;
Raina, S ;
Lloubès, R .
JOURNAL OF BACTERIOLOGY, 1998, 180 (18) :4872-4878
[9]   Structures of gram-negative cell walls and their derived membrane vesicles [J].
Beveridge, TJ .
JOURNAL OF BACTERIOLOGY, 1999, 181 (16) :4725-4733
[10]   Protein selection and export via outer membrane vesicles [J].
Bonnington, K. E. ;
Kuehn, M. J. .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 2014, 1843 (08) :1612-1619