The application is centered on IgAl proteases, extracellular enzymes of bacteria that hydrolyze and thereby inactivate their only known substrate, human IgAl antibody proteins. IgA is the major antibody isotype in secretions and lysis by bacteria may be regarded as circumvention of an immune response which fosters virulence. This, however, has not been proven experimentally. We propose to test the hypothesis that colonization of the neonatal and infant oral, pharyngeal and intestinal surfaces by bacteria, with concomitant maturation of the infant's own mucosal secretory immune system (also dominated by IgA secretions) subjects the IgA to lysis by colonizing sterptococci, Neissetia, Hemophilus and Bacteroides species. The application reviews the evidence that colonization and mucosal immune development occur together. It is further proposed that delivery of anti-IgAl proteases in milk of the nursing mother reduces or eliminates the detrimental effect of the enzyme on the child's local immune function. Preliminary work in our laboratory and confirmed elsewhere shows that polyclonal human colostrum and milk secretory IgA includes a subpopulation of high titre antibodies to some, but not all, IgAl proteases. The corollary of the hypothesis is that formula feeding does not provide this effect and therefore does not offer the protection against otitis media and other bacterial infections characteristic of the breast-fed infant. Our study subjects are to be mothers and their full-term infants, half of which are nursing, and half formula fed. The research involves bacteriology, protein chemistry and enzyme immunochemistry on specimens collected from these individuals.
| Plaut, A G (1988) Production and isolation of neissereal IgA proteases. Methods Enzymol 165:117-20 |
