Scale production and quality control of 23-valent pneumococcal polysaccharide vaccine

Objective: To improve the productivity and the quality of pneumococcal polysaccharide vaccine for expanding the scale of pneumococcal fermentation,increasing the yield of polysaccharides and reducing the endotoxin content of vaccine;to prepare and calibrate the pneumococcal polysaccharide reference products for enterprises and the serum for qualitatively and quantitatively detecting the 23-valent pneumococcal polysaccharide vaccine.Methods: Pneumococcal amplification fermentation was expanded,and the culture parameters,the feeding mode,feeding time of sugar and alkali in the cultivation were adjusted.The yield of purified polysaccharide was increased by adding the speed control and the temperature control,adjusting the ethanol concentration in the subparagraph ethanol precipitation process,and controlling the various technical parameters in the phenol extraction process.The endotoxin content in pneumococcal polysaccharide vaccine was reduced by controlling the main raw materials used in the production process and standardizing the behavior of operators.Rabbits and rats were immunized by polysaccharide to obtain the standard serum.Results: Pneumococcal fermentation volume increased from 500 to 1 000 L.Average yield of purified polysaccharides was more than 15%.Average endotoxin content was less than 20 EU·mL-1.The polysaccharide that met the 23-valent polysaccharide pneumococcal polysaccharide vaccine quality standards had been prepared.Three monoclonal antibodies and 6 polyclonal antibodies had been prepared.Conclusion: The yield of 23-valent pneumococcal polysaccharide vaccine is increased,and the quality is improved.The progress in domestic standard reference develops rapidly.