期刊
BIOSCIENCE REPORTS
卷 38, 期 -, 页码 -出版社
PORTLAND PRESS LTD
DOI: 10.1042/BSR20180238
关键词
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资金
- National Institute of Allergy and Infectious Diseases
- National Institutes of Health
- Department of Health and Human Services [HHSN272200700058C, HHSN272201200026C]
- Biological E. Limited, Hyderabad, India
It is established that the immunogenicity of polysaccharides is enhanced by coupling them to carrier proteins. Cross reacting material (CRM197), a nontoxic variant of diphtheria toxin (DT) is widely used carrier protein for polysaccharide conjugate vaccines. Conventionally, CRM197 is isolated by fermentation of Corynebacterium diphtheriae C7 (beta(197)) cultures, which often suffers from low yield. Recently, several recombinant approaches have been reported with robust processes and higher yields, which will improve the affordability of CRM197-based vaccines. Vaccine manufacturers require detailed analytical information to ensure that the CRM197 meets quality standards and regulatory requirements. In the present manuscript we have described detailed structural characteristics of Escherichia coli based recombinant CRM197 (rCRM(197)) carrier protein. The crystal structure of the E. coli based rCRM(197) was found to be identical with the reported crystal structure of the C7 CRM197 produced in C. diphtheriae C7 strain (Protein Data Bank (PDB) ID: 4EA0). The crystal structure of rCRM(197) was determined at 2.3 angstrom resolution and structure was submitted to the PDB with accession number ID 5I82. This is the first report of a crystal structure of E. coli derived recombinant CRM197 carrier protein. Furthermore, the rCRM(197) was conjugated to Vi polysaccharide to generate Typhoid conjugate vaccine (Vi- rCRM(197)) and its immunogenicity was evaluated in Balb/C Mice. The Vi-rCRM(197) conjugate vaccine was found to generate strong primary alpha-Vi antibody response and also showed a booster response after subsequent vaccination in mice. Overall data suggest that E. coli based recombinant CRM197 exhibits structural and immunological similarity with the C7 CRM197 and can be used as a carrier protein in conjugate vaccine development.
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