Evaluation of the non-toxic mutant of the diphtheria toxin K51E/E148K as carrier protein for meningococcal vaccines
Diphtheria toxin mutant CRM197 is a common carrier protein for glycoconjugate vaccines, which has been proven an effective protein vector for, among others, meningococcal carbohydrates. The wide-range use of this protein in massive vaccine production requires constant increase of production yields a...
| প্রধান লেখক: | , , , , , , , , |
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| বিন্যাস: | Journal article |
| ভাষা: | English |
| প্রকাশিত: |
Elsevier
2016
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| _version_ | 1826293467273232384 |
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| author | Pecetta, S Vijayakrishnan, B Romano, M Proietti, D Surdo, P Balocchi, C Mori, E Davis, B Berti, F |
| author_facet | Pecetta, S Vijayakrishnan, B Romano, M Proietti, D Surdo, P Balocchi, C Mori, E Davis, B Berti, F |
| author_sort | Pecetta, S |
| collection | OXFORD |
| description | Diphtheria toxin mutant CRM197 is a common carrier protein for glycoconjugate vaccines, which has been proven an effective protein vector for, among others, meningococcal carbohydrates. The wide-range use of this protein in massive vaccine production requires constant increase of production yields and adaptability to an ever-growing market. Here we compare CRM197 with the alternative diphtheria non-toxic variant DT-K51E/E148K, an inactive mutant that can be produced in the periplasm of Escherichia coli. Biophysical characterization of DT-K51E/E148K suggested high similarity with CRM197, with main differences in their alpha-helical content, and a suitable purity for conjugation and vaccine preparation. Meningococcal serogroup A (MenA) glycoconjugates were synthesized using CRM197 and DT-K51E/E148K as carrier proteins, obtaining the same conjugation yields and comparable biophysical profiles. Mice were then immunized with these CRM197 and DT-K51E/E148K conjugates, and essentially identical immunogenic and protective effects were observed. Overall, our data indicate that DT-K51E/E148K is a readily produced protein that now allows the added flexibility of E. coli production in vaccine development and that can be effectively used as protein carrier for a meningococcal conjugate vaccine. |
| first_indexed | 2024-03-07T03:30:33Z |
| format | Journal article |
| id | oxford-uuid:ba8eb021-70e5-41b1-b92a-c5c1ea32f9c5 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:30:33Z |
| publishDate | 2016 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:ba8eb021-70e5-41b1-b92a-c5c1ea32f9c52022-03-27T05:10:44ZEvaluation of the non-toxic mutant of the diphtheria toxin K51E/E148K as carrier protein for meningococcal vaccinesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:ba8eb021-70e5-41b1-b92a-c5c1ea32f9c5EnglishSymplectic Elements at OxfordElsevier2016Pecetta, SVijayakrishnan, BRomano, MProietti, DSurdo, PBalocchi, CMori, EDavis, BBerti, FDiphtheria toxin mutant CRM197 is a common carrier protein for glycoconjugate vaccines, which has been proven an effective protein vector for, among others, meningococcal carbohydrates. The wide-range use of this protein in massive vaccine production requires constant increase of production yields and adaptability to an ever-growing market. Here we compare CRM197 with the alternative diphtheria non-toxic variant DT-K51E/E148K, an inactive mutant that can be produced in the periplasm of Escherichia coli. Biophysical characterization of DT-K51E/E148K suggested high similarity with CRM197, with main differences in their alpha-helical content, and a suitable purity for conjugation and vaccine preparation. Meningococcal serogroup A (MenA) glycoconjugates were synthesized using CRM197 and DT-K51E/E148K as carrier proteins, obtaining the same conjugation yields and comparable biophysical profiles. Mice were then immunized with these CRM197 and DT-K51E/E148K conjugates, and essentially identical immunogenic and protective effects were observed. Overall, our data indicate that DT-K51E/E148K is a readily produced protein that now allows the added flexibility of E. coli production in vaccine development and that can be effectively used as protein carrier for a meningococcal conjugate vaccine. |
| spellingShingle | Pecetta, S Vijayakrishnan, B Romano, M Proietti, D Surdo, P Balocchi, C Mori, E Davis, B Berti, F Evaluation of the non-toxic mutant of the diphtheria toxin K51E/E148K as carrier protein for meningococcal vaccines |
| title | Evaluation of the non-toxic mutant of the diphtheria toxin K51E/E148K as carrier protein for meningococcal vaccines |
| title_full | Evaluation of the non-toxic mutant of the diphtheria toxin K51E/E148K as carrier protein for meningococcal vaccines |
| title_fullStr | Evaluation of the non-toxic mutant of the diphtheria toxin K51E/E148K as carrier protein for meningococcal vaccines |
| title_full_unstemmed | Evaluation of the non-toxic mutant of the diphtheria toxin K51E/E148K as carrier protein for meningococcal vaccines |
| title_short | Evaluation of the non-toxic mutant of the diphtheria toxin K51E/E148K as carrier protein for meningococcal vaccines |
| title_sort | evaluation of the non toxic mutant of the diphtheria toxin k51e e148k as carrier protein for meningococcal vaccines |
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