Multifaceted characterization of recombinant protein-based vaccines : An immunochemical toolbox for epitope-specific analyses of the hepatitis E vaccine
Copyright © 2018 Elsevier Ltd. All rights reserved..
The integrity of functional epitopes is a critical quality attribute for recombinant protein based vaccines since the presence of these native-like epitopes is the structural basis for vaccines to elicit functional antibodies. To demonstrate the quality and quantity of functional epitopes on vaccine antigens, a toolbox of assessing antigen characteristics is essential. Among the physicochemical, biophysical, immunochemical and in vivo potency analyses, the epitope-specific assays are most critical assessment of the antigen functionality. In this study, we used hepatitis E virus vaccine as an example to illustrated how the monoclonal antibody (mAb) based immunochemical assays were established for in-depth and multifaceted antigen characterization. A large panel of mAbs were developed and characterized using epitope clustering analysis. A subset of these mAbs recognizing non-overlapping epitopes were chosen to be used for assay development. Orthogonal methods, including surface plasma resonance-based BIAcore, solution competitive ELISA and sandwich ELISA, were developed for the antigenicity assessment. The sandwich ELISA with a pair of mAbs, recognizing two different epitopes, was used to assess the accelerated antigen stability, showing enhanced stability with adjuvant adsorption. Such a sandwich ELISA with robust performance has the potentials to be used for in vitro potency analysis to replace animal-based potency assay as product release test. In summary, using hepatitis E vaccine as an example, we demonstrated the importance and establishment of a mAb-based immunochemical toolbox for multifaceted antigen characterization. This is particularly important to demonstrate the successful reconstruction of the native-like and functional epitopes on a recombinant antigen post expression and purification. These epitope-specific and multifaceted assays serve as critical tools for process monitoring or lot consistency tests in support of vaccine development and manufacturing.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2018 |
|---|---|
| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:36 |
|---|---|
| Enthalten in: |
Vaccine - 36(2018), 50 vom: 29. Nov., Seite 7650-7658 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Wang, Xin [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Antibodies, Monoclonal |
|---|
| Anmerkungen: |
Date Completed 22.04.2019 Date Revised 22.04.2019 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.vaccine.2018.10.089 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM29030007X |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM29030007X | ||
| 003 | DE-627 | ||
| 005 | 20231225064431.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2018 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.vaccine.2018.10.089 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0967.xml |
| 035 | |a (DE-627)NLM29030007X | ||
| 035 | |a (NLM)30396752 | ||
| 035 | |a (PII)S0264-410X(18)31486-5 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Wang, Xin |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Multifaceted characterization of recombinant protein-based vaccines |b An immunochemical toolbox for epitope-specific analyses of the hepatitis E vaccine |
| 264 | 1 | |c 2018 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 22.04.2019 | ||
| 500 | |a Date Revised 22.04.2019 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2018 Elsevier Ltd. All rights reserved. | ||
| 520 | |a The integrity of functional epitopes is a critical quality attribute for recombinant protein based vaccines since the presence of these native-like epitopes is the structural basis for vaccines to elicit functional antibodies. To demonstrate the quality and quantity of functional epitopes on vaccine antigens, a toolbox of assessing antigen characteristics is essential. Among the physicochemical, biophysical, immunochemical and in vivo potency analyses, the epitope-specific assays are most critical assessment of the antigen functionality. In this study, we used hepatitis E virus vaccine as an example to illustrated how the monoclonal antibody (mAb) based immunochemical assays were established for in-depth and multifaceted antigen characterization. A large panel of mAbs were developed and characterized using epitope clustering analysis. A subset of these mAbs recognizing non-overlapping epitopes were chosen to be used for assay development. Orthogonal methods, including surface plasma resonance-based BIAcore, solution competitive ELISA and sandwich ELISA, were developed for the antigenicity assessment. The sandwich ELISA with a pair of mAbs, recognizing two different epitopes, was used to assess the accelerated antigen stability, showing enhanced stability with adjuvant adsorption. Such a sandwich ELISA with robust performance has the potentials to be used for in vitro potency analysis to replace animal-based potency assay as product release test. In summary, using hepatitis E vaccine as an example, we demonstrated the importance and establishment of a mAb-based immunochemical toolbox for multifaceted antigen characterization. This is particularly important to demonstrate the successful reconstruction of the native-like and functional epitopes on a recombinant antigen post expression and purification. These epitope-specific and multifaceted assays serve as critical tools for process monitoring or lot consistency tests in support of vaccine development and manufacturing | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Antibodies, Monoclonal |2 NLM | |
| 650 | 7 | |a Epitopes |2 NLM | |
| 650 | 7 | |a Hepatitis Antibodies |2 NLM | |
| 650 | 7 | |a Vaccines, Subunit |2 NLM | |
| 650 | 7 | |a Vaccines, Synthetic |2 NLM | |
| 650 | 7 | |a Viral Hepatitis Vaccines |2 NLM | |
| 700 | 1 | |a Li, Min |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Zhijie |e verfasserin |4 aut | |
| 700 | 1 | |a Pan, Huirong |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Zimin |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Zizheng |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Shaowei |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Xia, Ningshao |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Qinjian |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Vaccine |d 1985 |g 36(2018), 50 vom: 29. Nov., Seite 7650-7658 |w (DE-627)NLM012600105 |x 1873-2518 |7 nnns |
| 773 | 1 | 8 | |g volume:36 |g year:2018 |g number:50 |g day:29 |g month:11 |g pages:7650-7658 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.vaccine.2018.10.089 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 36 |j 2018 |e 50 |b 29 |c 11 |h 7650-7658 | ||