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.