Our studies have shown that Campylobacter jejuni (C. jejuni) is an important bacterial enteric pathogen in laboratory housed non-human primates. This enteropathogen causes colitis. Because diarrhea is an important disease in laboratory primates, our objective is to enhance animal care and well being by obtaining a better understanding of this important disease problem. The studies will enable better methods of disease control and prevention.
The aim of these studies is to determine and characterize the protective immune response. For these studies, the pathologic changes in the colon will be studied during the initial stages of infection to determine the host-parasite interaction with respect to adherence and invasion; and how this results in the actual epithelial cell damage. In vitro cell adherence assays with C. jejuni will be studied using the Caco-2 cell line. Abrogation of adherence by inhibition with monospecific and monoclonal antibodies will identify specific adhesin proteins. The mechanism of the host protective immune response in the intestinal tract will be studied by determining: firstly, the ontogeny of the secretory IgA (SIgA) immune system in infant M. fascicularis, and secondly, by studying the SIgA response after experimental challenge. Morphologic studies will be conducted to determine whether immunity correlates with abrogation of adherence upon rechallenge with pathogenic strains of homologous and heterologous C. jejuni. Gnotobiotic infants will be challenged with C. jejuni strain 81-176 to provide a source of pure C. jejuni expressing virulence factors during active disease. These organisms will be compared with C. jejuni grown on artificial media. Following identification of specific protective antigens, the proteins will be purified and the localization on the bacterial outer membrane or pilin appendages will be determined by immunoelectron microscopy. The antigenic relationship between protective antigens of different strains of C. jejuni and C. coli will be analyzed by ELISA, immunoblot and adherence inhibition assays. The information from the study will provide essential knowledge and reagents needed to develop vaccines for disease prevention.
