Research Interests

I have applied bacteriology and simple chemistry to development of vaccines against bacterial infections of infancy, particularly bacteria in which the capsular polysaccharide (CP) interferes with phagocytic clearance. Antibody to CP is protective, but the immune response to CP matures slowly. Along with other workers, I researched conjugation of CP to immunogenic carrier proteins, permitting early-life antibody induction. My approach was used for the first "conjugate" vaccines licensed for 2-month-old infants against meningitis and other life-threatening infections by haemophili, meningococci, and pneumococci. The substantial decline in Haemophilus disease prompted the 1996 Lasker Clinical Award and Pasteur Award to JB Robbins, R Schneerson, DH Smith, and me. Pneumococcus infections of infancy are prevalent and deadly in third-world settings, but conjugate vaccines are too expensive for nations most afflicted. Since 1996 I have worked with R Malley, reviving an inexpensive alternative consisting of killed bacteria--technology readily transferable to developing-world manufacturers. This was protective in preclinical testing, partly through an unexpected antibody-independent, CD4+ T lymphocyte-dependent mechanism, mediated through pro-phagocytic activity of the cytokine IL17A and attributable to TLR agonists within the vaccine. Approval for clinical testing is being sought.

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Section 44: Microbial Biology