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.

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