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 the prevention of such diseases. 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. These 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, non-typhoidal Salmonella, Shigella, and Vibrio cholerae. The Vi capsular polysaccharide conjugate was over 90 percent effective against typhoid fever in two- to five-year-olds. Based on a level of anti-Vi that the LDMI found to be protective, clinical trials are under way to evaluate the immunogenicity of Vi-rEPA, which is being administered concurrently with DTP during the primary injection of infants. By producing a non-toxic mutant Shigella toxin and conjugating it to the capsular polysaccharide of E. coli O157, LDMI researchers produced an experimental vaccine against this structure; E. coli O157 causes the often fatal hemolytic uremic syndrome, especially in small children. The investigational vaccine has proven to be safe and immunogenic in infants, and clinical trials for efficacy are now being planned. A conjugate vaccine against Staphylococcus aureus, the cause of many hospital-acquired infections, has been tested successfully in hemodialysis patients, who are at increased risk of infection by this pathogen. In an effort to produce an anthrax vaccine with fewer side effects than those associated with the currently available vaccine, LDMI researchers in collaboration with researchers at NIDDK have produced on an industrial scale a recombinant protein antigen vaccine against Bacillus anthracis. Now in a Phase 1 trial, the vaccine has elicited levels of neutralizing antibody in mice comparable to those observed with the currently available AVA vaccine. Work is in progress to produce a conjugate vaccine against Borrelia burgdorferi, the causative agent of Lyme disease.