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

doi:10.1021/pr301208g

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 journal › Article › Academic › peer-review

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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 language	English
Pages (from-to)	1898-1908
Number of pages	11
Journal	Journal of Proteome Research
Volume	12
DOIs	https://doi.org/10.1021/pr301208g
Publication status	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1021/pr301208g

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@article{2056149811b545a98c33c16c5d05a93f,

title = "Quantitative Proteomics Reveals Distinct Differences in the Protein Content of Outer Membrane Vesicle Vaccines",

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",

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

author = "{van de Waterbeemd}, B. and G.P.M. Mommen and J.L.A. Pennings and M.H.M. Eppink and R.H. Wijffels and {van der Pol}, L.A. and {de Jong}, A.P.J.M.",

year = "2013",

doi = "10.1021/pr301208g",

language = "English",

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journal = "Journal of Proteome Research",

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publisher = "American Chemical Society",

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TY - JOUR

T1 - Quantitative Proteomics Reveals Distinct Differences in the Protein Content of Outer Membrane Vesicle Vaccines

AU - van de Waterbeemd, B.

AU - Mommen, G.P.M.

AU - Pennings, J.L.A.

AU - Eppink, M.H.M.

AU - Wijffels, R.H.

AU - van der Pol, L.A.

AU - de Jong, A.P.J.M.

PY - 2013

Y1 - 2013

N2 - 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

AB - 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

KW - meningitidis serogroup-b

KW - h-binding-protein

KW - serum bactericidal activity

KW - n-terminal peptides

KW - neisseria-meningitidis

KW - meningococcal disease

KW - mass-spectrometry

KW - positional proteomics

KW - attenuated endotoxin

KW - identification

U2 - 10.1021/pr301208g

DO - 10.1021/pr301208g

M3 - Article

SN - 1535-3893

VL - 12

SP - 1898

EP - 1908

JO - Journal of Proteome Research

JF - Journal of Proteome Research

ER -

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

Abstract

Keywords

UN SDGs

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