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Homogeneous Glycoconjugate Produced by Combined Unnatural Amino Acid Incorporation and Click-Chemistry for Vaccine Purposes
Published on: December 19, 2020
Process development and immunogenicity studies on a serogroup 'X' Meningococcal polysaccharide conjugate vaccine
Srinivas Reddy Chilukuri1, Peddi Reddy1, Nikhil Avalaskar1
1Research and Development Department, Serum Institute of India Ltd, Serum Biopharma Park, 212/2, Hadapsar, Pune 411028, Maharashtra, India.
Abstract:
Meningococcal group X (MenX) is responsible for recent outbreaks of meningitis reported in sub-Saharan region of Africa. Although protective vaccines are available for meningitis, they are not effective against MenX. An efficacious, monovalent conjugate vaccine was designed against MenX and a fed-batch fermentation process was developed. The MenX polysaccharide (PS) was purified and yield estimated to be 15-fold higher than the reported elsewhere. Structure of MenX polysaccharide was confirmed by (1)H, (13)C NMR spectroscopy analysis. Molecular weight of PS was found to be 310 kDa using HPLC-SEC coupled to refractive index (RI) detector. The MenX-Tetanus toxoid (TT) monovalent conjugate proved to be highly immunogenic in mice, and the bactericidal titers of MenX-TT conjugate were 10-fold higher than native PS. Increasing the dose of MenX-TT conjugate from 0.5 μg to 1.0 μg induced an 8-fold higher antibody titer as well as serum bactericidal titer. The current work suggests that the MenX-TT conjugate is a candidate vaccine against meningitis caused by Meningococcal group X strains.
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