A continuous method for preparing proteosome-amphiphilic determinant vaccines for parenteral or mucosal administration using diafiltration or ultrafiltration technology. The amphiphilic determinants include lipopolysaccharides from gram negative bacteria, e.g. S. flexneri, P. shigelloides and S. sonnei. Proteosomes are obtained from group B type 2b meningococci. The active proteosome-amphiphilic determinant complexes (non-covalent complexes) of the vaccine are formed using diafiltration or ultrafiltration to remove the detergent under non-static conditions. The use of diafiltration or ultrafiltration decreases processing time and the opportunity for contamination and further permits the use of ambient temperature and efficient scale-up. In addition, the process permits the reliable and continuous monitoring of the dializate which enhances the efficiency of the entire process. The time of dialysis for the production of a lot of vaccine is reduced from 7-10 days to less than 72 hours and usually less than 48 or 24 hours. The use of the process optimizes the presence of each antigenic component in the preparation of multivalent vaccines.

 
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