laboratory of
developmental and molecular immunity
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John B. Robbins, MD,
Chief The Laboratory of Developmental and Molecular
Immunity (LDMI) studies the pathogenesis of and immunity to bacterial
diseases, especially those of infants and children, with the overall objective
of developing vaccines for their prevention. Given that almost all pathogens
of healthy individuals are inhabitants of humans only, the LDMI brings its
investigational vaccines to clinical evaluation for safety, immunogenicity,
and, ultimately, efficacy as soon as possible. The LDMI’s research is
guided by the principle that “the proper study of mankind is
man.” 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 the vaccine have now yielded conjugate vaccines against Salmonella typhi, nontyphoidal salmonellae, shigellae, and Vibrio cholerae; the vaccines are now in field tests. 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 the NIDDK, has been shown to elicit comparable levels of neutralizing antibody in mice and is now under review by the Food and Drug Administration. Work is in progress to produce a conjugate vaccine against Borrelia burgdorferi, the causative agent of Lyme disease. |