白喉毒素
突变体
白喉
结合
微生物学
白喉棒状杆菌
大肠杆菌
毒素
脑膜炎奈瑟菌
糖复合物
生物
化学
病毒学
生物化学
接种疫苗
细菌
遗传学
基因
数学分析
数学
作者
Simone Pecetta,Balakumar Vijayakrishnan,Maria Romano,Daniela Proietti,Paola Lo Surdo,Cristiana Balocchi,Elena Mori,Brandi Davis,Francesco Berti
出处
期刊:Vaccine
[Elsevier]
日期:2016-03-01
卷期号:34 (11): 1405-1411
被引量:5
标识
DOI:10.1016/j.vaccine.2016.01.040
摘要
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.
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