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

Wouter S P Jong; Maria H Daleke-Schermerhorn; David Vikström; Corinne M Ten Hagen-Jongman; Karin de Punder; Nicole N van der Wel; Carolien E van de Sandt; Guus F Rimmelzwaan; Frank Follmann; Else Marie Agger; Peter Andersen; Jan-Willem de Gier; Joen Luirink

doi:10.1186/s12934-014-0162-8

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

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

Authors

Wouter S P Jong^{1

2}, Maria H Daleke-Schermerhorn^{3

4}, David Vikström^{5

6}, Corinne M Ten Hagen-Jongman^{7

8}, Karin de Punder^{9

10}, Nicole N van der Wel^{11

12}, Carolien E van de Sandt¹³, Guus F Rimmelzwaan¹⁴, Frank Follmann¹⁵, Else Marie Agger¹⁶, Peter Andersen¹⁷, Jan-Willem de Gier^{18

19}, Joen Luirink^{20

21}

Affiliations

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. [email protected].
² Abera Bioscience AB, SE-111 45, Stockholm, Sweden. [email protected].
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. [email protected].
⁴ Abera Bioscience AB, SE-111 45, Stockholm, Sweden. [email protected].
⁵ Xbrane Bioscience AB, SE-111 45, Stockholm, Sweden. [email protected].
⁶ Department of Biochemistry and Biophysics, Center for Biomembrane Research, Stockholm University, SE-106 91, Stockholm, Sweden. [email protected].
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. [email protected].
⁸ Abera Bioscience AB, SE-111 45, Stockholm, Sweden. [email protected].
⁹ The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, 1066, CX, Amsterdam, The Netherlands. [email protected].
¹⁰ Present Address: Institute for Medical Psychology, Charité Universitätsmedizin, 10117, Berlin, Germany. [email protected].
¹¹ The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, 1066, CX, Amsterdam, The Netherlands. [email protected].
¹² Present Address: Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, 1105, AZ, Amsterdam, The Netherlands. [email protected].
¹³ Department of Viroscience, Erasmus Medical Center, 3015, GE, Rotterdam, The Netherlands. [email protected].
¹⁴ Department of Viroscience, Erasmus Medical Center, 3015, GE, Rotterdam, The Netherlands. [email protected].
¹⁵ Department of Infectious Disease & Immunology, Statens Serum Institut, Copenhagen, Denmark. [email protected].
¹⁶ Department of Infectious Disease & Immunology, Statens Serum Institut, Copenhagen, Denmark. [email protected].
¹⁷ Department of Infectious Disease & Immunology, Statens Serum Institut, Copenhagen, Denmark. [email protected].
¹⁸ Xbrane Bioscience AB, SE-111 45, Stockholm, Sweden. [email protected].
¹⁹ Department of Biochemistry and Biophysics, Center for Biomembrane Research, Stockholm University, SE-106 91, Stockholm, Sweden. [email protected].
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. [email protected].
²¹ Abera Bioscience AB, SE-111 45, Stockholm, Sweden. [email protected].

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antigens, Bacterial* / genetics
Antigens, Bacterial* / metabolism
Antigens, Viral* / genetics
Antigens, Viral* / metabolism
Bacterial Secretion Systems*
Bacterial Vaccines* / genetics
Bacterial Vaccines* / metabolism
Chlamydia trachomatis / genetics
Endopeptidases* / genetics
Endopeptidases* / metabolism
Escherichia coli* / genetics
Escherichia coli* / metabolism
Influenza A virus / genetics
Influenza Vaccines* / genetics
Influenza Vaccines* / metabolism
Mycobacterium tuberculosis / genetics
Salmonella typhimurium* / genetics
Salmonella typhimurium* / metabolism

Substances

Antigens, Bacterial
Antigens, Viral
Bacterial Secretion Systems
Bacterial Vaccines
Influenza Vaccines
Endopeptidases
hemoglobin protease Hbp