Proteomics-driven Antigen Discovery for Development of Vaccines Against Gonorrhea Public Deposited

http://ir.library.oregonstate.edu/concern/articles/r494vm928

Supplemental material is available online at:  http://www.mcponline.org/content/15/7/2338/suppl/DC1

To the best of our knowledge, one or more authors of this paper were federal employees when contributing to this work. This is the publisher’s final pdf. The published article is copyrighted by The American Society for Biochemistry and Molecular Biology and can be found at:  http://www.mcponline.org/content/15/7/2338

Descriptions

Attribute NameValues
Creator
Abstract or Summary
  • Expanding efforts to develop preventive gonorrhea vaccines is critical because of the dire possibility of untreatable gonococcal infections. Reverse vaccinology, which includes genome and proteome mining, has proven very successful in the discovery of vaccine candidates against many pathogenic bacteria. However, progress with this approach for a gonorrhea vaccine remains in its infancy. Accordingly, we applied a comprehensive proteomic platform—isobaric tagging for absolute quantification coupled with two-dimensional liquid chromatography and mass spectrometry—to identify potential gonococcal vaccine antigens. Our previous analyses focused on cell envelopes and naturally released membrane vesicles derived from four different Neisseria gonorrhoeae strains. Here, we extended these studies to identify cell envelope proteins of N. gonorrhoeae that are ubiquitously expressed and specifically induced by physiologically relevant environmental stimuli: oxygen availability, iron deprivation, and the presence of human serum. Together, these studies enabled the identification of numerous potential gonorrhea vaccine targets. Initial characterization of five novel vaccine candidate antigens that were ubiquitously expressed under these different growth conditions demonstrated that homologs of BamA (NGO1801), LptD (NGO1715), and TamA (NGO1956), and two uncharacterized proteins, NGO2054 and NGO2139, were surface exposed, secreted via naturally released membrane vesicles, and elicited bactericidal antibodies that cross-reacted with a panel of temporally and geographically diverse isolates. In addition, analysis of polymorphisms at the nucleotide and amino acid levels showed that these vaccine candidates are highly conserved among N. gonorrhoeae strains. Finally, depletion of BamA caused a loss of N. gonorrhoeae viability, suggesting it may be an essential target. Together, our data strongly support the use of proteomics-driven discovery of potential vaccine targets as a sound approach for identifying promising gonococcal antigens.
Resource Type
DOI
Date Available
Date Issued
Citation
  • Zielke, R. A., Wierzbicki, I. H., Baarda, B. I., Gafken, P. R., Soge, O. O., Holmes, K. K., ... & Sikora, A. E. (2016). Proteomics-driven antigen discovery for development of vaccines against gonorrhea. Molecular & Cellular Proteomics, 15(7), 2338-2355. doi:10.1074/mcp.M116.058800
Series
Rights Statement
Funding Statement (additional comments about funding)
Publisher
Peer Reviewed
Language
Replaces
Additional Information
  • description.provenance : Submitted by Open Access (openaccess@library.oregonstate.edu) on 2016-08-10T20:14:14Z No. of bitstreams: 1 ZielkeProteomicsDrivenAntigen.pdf: 1138524 bytes, checksum: 1699bb13ed345188843d7177c9910bea (MD5)
  • description.provenance : Made available in DSpace on 2016-08-11T15:59:46Z (GMT). No. of bitstreams: 2 krauserp896290639.zip: 1046798 bytes, checksum: 2ce78c7b85c56b14a2462e4429f7f501 (MD5) ZielkeProteomicsDrivenAntigen.pdf: 1138524 bytes, checksum: 1699bb13ed345188843d7177c9910bea (MD5) Previous issue date: 2016-07
  • description.provenance : Approved for entry into archive by Patricia Black(patricia.black@oregonstate.edu) on 2016-08-11T15:59:46Z (GMT) No. of bitstreams: 2 krauserp896290639.zip: 1046798 bytes, checksum: 2ce78c7b85c56b14a2462e4429f7f501 (MD5) ZielkeProteomicsDrivenAntigen.pdf: 1138524 bytes, checksum: 1699bb13ed345188843d7177c9910bea (MD5)

Relationships

Parents:

This work has no parents.

Last modified

Downloadable Content

Download PDF

Items