Quantitative Proteomics Reveals Distinct Differences in the Protein Content of Outer Membrane Vesicle Vaccines

B. van de Waterbeemd, G.P.M. Mommen, J.L.A. Pennings, M.H.M. Eppink, R.H. Wijffels, L.A. van der Pol, A.P.J.M. de Jong

Research output: Contribution to journalArticleAcademicpeer-review

34 Citations (Scopus)

Abstract

At present, only vaccines containing outer membrane vesicles (OMV) have successfully stopped Neisseria meningitidis serogroup B epidemics. These vaccines however require detergent-extraction to remove endotoxin, which changes immunogenicity and causes production difficulties. To investigate this in more detail, the protein content of detergent-extracted OMV is compared with two detergent-free alternatives. A novel proteomics strategy has been developed that allows quantitative analysis of many biological replicates despite inherent multiplex restrictions of dimethyl labeling. This enables robust statistical analysis of relative protein abundance. The comparison with detergentextracted OMV reveales that detergent-free OMV are enriched with membrane (lipo)proteins and contain less cytoplasmic proteins due to a milder purification process. These distinct protein profiles are substantiated with serum blot proteomics, confirming enrichment with immunogenic proteins in both detergent-free alternatives. Therefore, the immunogenic protein content of OMV vaccines depends at least partially on the purification process. This study demonstrates that detergent-free OMV have a preferred composition. KEYWORDS: quantitative proteomics, common reference, N-proteomics, PTAG, OMV, outer membrane vesicles, vaccine, immunogenicity
Original languageEnglish
Pages (from-to)1898-1908
Number of pages11
JournalJournal of Proteome Research
Volume12
DOIs
Publication statusPublished - 2013

Keywords

  • meningitidis serogroup-b
  • h-binding-protein
  • serum bactericidal activity
  • n-terminal peptides
  • neisseria-meningitidis
  • meningococcal disease
  • mass-spectrometry
  • positional proteomics
  • attenuated endotoxin
  • identification

Fingerprint Dive into the research topics of 'Quantitative Proteomics Reveals Distinct Differences in the Protein Content of Outer Membrane Vesicle Vaccines'. Together they form a unique fingerprint.

Cite this