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Microb Cell Fact. 2014 Nov 25;13:162. doi: 10.1186/s12934-014-0162-8.

An autotransporter display platform for the development of multivalent recombinant bacterial vector vaccines.

Author information

1
Department of Molecular Cell Biology, Section Molecular Microbiology, Faculty of Earth and Life Sciences, VU University, De Boelelaan 1085, 1081, HV, Amsterdam, The Netherlands. w.s.p.jong@vu.nl.
2
Abera Bioscience AB, SE-111 45, Stockholm, Sweden. w.s.p.jong@vu.nl.
3
Department of Molecular Cell Biology, Section Molecular Microbiology, Faculty of Earth and Life Sciences, VU University, De Boelelaan 1085, 1081, HV, Amsterdam, The Netherlands. maria.daleke@aberabio.com.
4
Abera Bioscience AB, SE-111 45, Stockholm, Sweden. maria.daleke@aberabio.com.
5
Xbrane Bioscience AB, SE-111 45, Stockholm, Sweden. david.vikstrom@xbrane.com.
6
Department of Biochemistry and Biophysics, Center for Biomembrane Research, Stockholm University, SE-106 91, Stockholm, Sweden. david.vikstrom@xbrane.com.
7
Department of Molecular Cell Biology, Section Molecular Microbiology, Faculty of Earth and Life Sciences, VU University, De Boelelaan 1085, 1081, HV, Amsterdam, The Netherlands. c.m.ten.hagen-jongman@vu.nl.
8
Abera Bioscience AB, SE-111 45, Stockholm, Sweden. c.m.ten.hagen-jongman@vu.nl.
9
The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, 1066, CX, Amsterdam, The Netherlands. karin.de-punder@charite.de.
10
Present Address: Institute for Medical Psychology, Charité Universitätsmedizin, 10117, Berlin, Germany. karin.de-punder@charite.de.
11
The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, 1066, CX, Amsterdam, The Netherlands. N.N.vanderWel@amc.uva.nl.
12
Present Address: Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, 1105, AZ, Amsterdam, The Netherlands. N.N.vanderWel@amc.uva.nl.
13
Department of Viroscience, Erasmus Medical Center, 3015, GE, Rotterdam, The Netherlands. c.vandesandt@erasmusmc.nl.
14
Department of Viroscience, Erasmus Medical Center, 3015, GE, Rotterdam, The Netherlands. g.rimmelzwaan@erasmusmc.nl.
15
Department of Infectious Disease & Immunology, Statens Serum Institut, Copenhagen, Denmark. FRF@ssi.dk.
16
Department of Infectious Disease & Immunology, Statens Serum Institut, Copenhagen, Denmark. EAG@ssi.dk.
17
Department of Infectious Disease & Immunology, Statens Serum Institut, Copenhagen, Denmark. PA@ssi.dk.
18
Xbrane Bioscience AB, SE-111 45, Stockholm, Sweden. degier@dbb.su.se.
19
Department of Biochemistry and Biophysics, Center for Biomembrane Research, Stockholm University, SE-106 91, Stockholm, Sweden. degier@dbb.su.se.
20
Department of Molecular Cell Biology, Section Molecular Microbiology, Faculty of Earth and Life Sciences, VU University, De Boelelaan 1085, 1081, HV, Amsterdam, The Netherlands. s.luirink@vu.nl.
21
Abera Bioscience AB, SE-111 45, Stockholm, Sweden. s.luirink@vu.nl.

Abstract

BACKGROUND:

The Autotransporter pathway, ubiquitous in Gram-negative bacteria, allows the efficient secretion of large passenger proteins via a relatively simple mechanism. Capitalizing on its crystal structure, we have engineered the Escherichia coli autotransporter Hemoglobin protease (Hbp) into a versatile platform for secretion and surface display of multiple heterologous proteins in one carrier molecule.

RESULTS:

As proof-of-concept, we demonstrate efficient secretion and high-density display of the sizeable Mycobacterium tuberculosis antigens ESAT6, Ag85B and Rv2660c in E. coli simultaneously. Furthermore, we show stable multivalent display of these antigens in an attenuated Salmonella Typhimurium strain upon chromosomal integration. To emphasize the versatility of the Hbp platform, we also demonstrate efficient expression of multiple sizeable antigenic fragments from Chlamydia trachomatis and the influenza A virus at the Salmonella cell surface.

CONCLUSIONS:

The successful efficient cell surface display of multiple antigens from various pathogenic organisms highlights the potential of Hbp as a universal platform for the development of multivalent recombinant bacterial vector vaccines.

PMID:
25421093
PMCID:
PMC4252983
DOI:
10.1186/s12934-014-0162-8
[Indexed for MEDLINE]
Free PMC Article

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