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| Effects of detoxification process on toxicity and foreign protein of tetanus toxoid and diphtheria toxoid | |
| Long, Zhen1; Wei, Chen2; Ross, Robert3; Luo, Xi4; Ma, Xiao2; Qi, Yingzi1; Chai, Ruiping1; Cao, Jianming1; Huang, Min1; Bo, Tao1 | |
| 2022-09-01 | |
| Source Publication | JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
 |
| ISSN | 1570-0232 |
| Volume | 1207Pages:10 |
| Abstract | Formaldehyde detoxification is a process for converting tetanus toxin (TT) and diphtheria toxin (DT) into tetanus toxoid (TTd) and diphtheria toxoid (DTd), respectively. The mechanism of this detoxification process has been investigated by several previous studies based on lab-scale toxoids. To obtain greater insights of the effects induced by formaldehyde, industrial TTd and DTd batches obtained from different detoxification processes were studied in this work. Using liquid chromatography-mass spectrometry (LC-MS), 15 and 20 repeatable formaldehyde-induced modification sites of TTd and DTd were identified, respectively. Toxoid which had a higher formaldehyde-induced modification rate observed by LC-MS, also had larger bands on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Aggregates which were observed on size exclusion chromatogram (SEC) were confirmed by SDS-PAGE and LC-MS. Formaldehyde detoxification also led to a decrease of isoelectric point (pI) values and an increase of retention on weak anion exchange (WAX) column. Specific toxicity tests were conducted to evaluate toxicity of the TTd and DTd samples obtained with different detoxification conditions. Results from the specific toxicity tests showed that all toxoids used in this study were qualified, including toxoids obtained from mild and drastic detoxification conditions. However, obtained from mild detoxification conditions had less aggregates and may lead to a higher degree of glycosylation in conjugate vaccines than the ones obtained from drastic detoxification conditions. Thus, we suggest that mild detoxification conditions should be used to obtain TTd and DTd. Furthermore, as well as studying the formaldehyde-induced modifications and toxicity in TTd and DTd, the effects of the detoxification process on foreign proteins were also investigated. An increase in foreign proteins were observed in the aggregate than in the monomer of the toxoids. Additionally, some foreign proteins in the monomer of the toxins transferred to the aggregate of toxoids due to the formation of cross-linking. To eliminate the risk of cross-linking foreign proteins to toxoids in vaccination programs, a purification process is necessary before the detoxification process and/or the use of toxoids in vaccines. |
| Keyword | Tetanus Diphtheria Conjugate vaccine DTP vaccine Mass spectrometry |
| DOI | 10.1016/j.jchromb.2022.123377 |
| Language | 英语 |
| WOS Keyword | FORMALDEHYDE-INDUCED MODIFICATIONS ; SEROLOGICAL POTENCY TEST ; THERMAL-STABILITY ; TOXIN ; IDENTIFICATION ; CHROMATOGRAPHY |
| Funding Project | Independent Research Project of the State Key Laboratory of Biochemical Engineering[2021ZZ03] |
| WOS Research Area | Biochemistry & Molecular Biology ; Chemistry |
| WOS Subject | Biochemical Research Methods ; Chemistry, Analytical |
| Funding Organization | Independent Research Project of the State Key Laboratory of Biochemical Engineering |
| WOS ID | WOS:000858771600008 |
| Publisher | ELSEVIER |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | http://ir.ipe.ac.cn/handle/122111/54812 |
| Collection | 中国科学院过程工程研究所 |
| Corresponding Author | Luo, Xi; Ma, Xiao |
| Affiliation | 1.ThermoFisher Sci Corp, Beijing 100080, Peoples R China 2.Natl Inst Food & Drug Control, Minist Hlth Res Qual & Standardizat Biotech Prod, Key Lab, Beijing 100050, Peoples R China 3.ThermoFisher Sci Corp, San Jose, CA 95134 USA 4.Chinese Acad Sci, Inst Proc Engn, State Key Lab Biochem Engn, Beijing 100190, Peoples R China |
| Recommended Citation GB/T 7714 | Long, Zhen,Wei, Chen,Ross, Robert,et al. Effects of detoxification process on toxicity and foreign protein of tetanus toxoid and diphtheria toxoid[J]. JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES,2022,1207:10. |
| APA | Long, Zhen.,Wei, Chen.,Ross, Robert.,Luo, Xi.,Ma, Xiao.,...&Bo, Tao.(2022).Effects of detoxification process on toxicity and foreign protein of tetanus toxoid and diphtheria toxoid.JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES,1207,10. |
| MLA | Long, Zhen,et al."Effects of detoxification process on toxicity and foreign protein of tetanus toxoid and diphtheria toxoid".JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES 1207(2022):10. |
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