An autotransporter display platform for the development of multivalent recombinant bacterial vector vaccines
Wouter SP Jong, Maria H Daleke-Schermerhorn, David Vikstom, 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
Microbial Cell Factories | BIOMED CENTRAL LTD | Published : 2014
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..View full abstract
Awarded by Colorado State University, USA
Awarded by European Union
The authors thank P. van Ulsen and W. Bitter for useful comments on the manuscript. T. Silhavy (Princeton University, USA) and X. Saelens (University of Ghent, Belgium) are acknowledged for providing antisera. DNA of M. tuberculosis H37Rv was obtained, in collaboration with B.J. Appelmelk, from J.T. Belisle (Colorado State University, USA) (contract No. AI-75320). This research was supported by the Dutch Technology Foundation STW (WSPJ and JL) and the European Union's Seventh Framework Programme [FP7/2007-2013] under Grant Agreement No: 280873 ADITEC (MHDS and JL). In addition, we acknowledge support from the Swedish Research Council (VR-M) and the Swedish Foundation for Strategic Research (SSF) through the Center for Biomembrane Research (JWdG).