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. A conjugate vaccine against Staphylococcus aureus, the cause of many hospital-acquired infections, has been tested successfully in hemodialysis patients, who are also at increased risk of infection by this pathogen. In an effort to produce an anthrax vaccine with fewer side effects than the currently available vaccine, a recombinant vaccine against Bacillus anthracis, produced on an industrial scale in collaboration with researchers at NIDDK, has been shown, in mice, to elicit levels of neutralizing antibody comparable to those elicited by the currently available vaccine.