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Members of the LDMI pioneered the development of a new generation of vaccines in which specific antigenic capsular polysaccharides are chemically conjugated to highly immunogenic but nonspecific proteins. The new conjugate vaccines, which confer T-cell dependence and booster responses to polysaccharide antigens, have been singularly successful, as exemplified by the H influenzae type b conjugate vaccine. H. influenzae type b meningitis (the most common cause of acquired mental retardation) has been virtually eliminated wherever the vaccine has been used. The principles and methods developed for this vaccine have now yielded conjugate vaccines against Salmonella typhi, nontyphoidal Salmonellae, Shigellae, and Vibrio cholerae, which are being field tested. By producing a nontoxic mutant shigella-like toxin and conjugating it to the capsular polysaccharide of E. coli 0157, LDMI researchers produced an experimental vaccine against this pathogen, which causes the often fatal hemolytic uremic syndrome, especially in small children.