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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.

Original publication

DOI

10.1016/j.vaccine.2016.01.040

Type

Journal article

Journal

Vaccine

Publication Date

08/03/2016

Volume

34

Pages

1405 - 1411

Keywords

CRM(197), Conjugate vaccines, DT-K51E/E148K, Diphtheria toxin mutant, Meningococcal vaccines, Animals, Antibodies, Bacterial, Bacterial Proteins, Diphtheria Toxin, Drug Carriers, Escherichia coli, Female, Immunity, Humoral, Meningococcal Vaccines, Mice, Mice, Inbred BALB C, Rabbits, Serum Bactericidal Antibody Assay, Vaccines, Conjugate