The design of a vaccine as a means to control Porphyromonas gingivalis will require knowledge of how to induce immunity to the various virulence factors of this organism. In this study, oral immunization in mice with live avirulent Salmonella typhimurium strains expressing the clone P. gingivalis hemagglutinin Hag B, will be used to examine the induction of immunity to these organisms. The optimum immunization regimen and kinetics for primary immunization with avirulent Salmonella carriers expressing P. gingivalis antigens including such factors as dosage, number and frequency of doses will be examined. The optimum regimen and the kinetics for boosting will also be determined. The responses in serum, saliva, bile, vaginal and gut washes and in fecal samples will be measured with respect to magnitude, duration and isotypic distribution in these compartments. Immune responses at the single cell level in spleen, gut lamina propria and salivary glands will be assessed and selected samples will be examined for IgG subclass distribution. The impact on cell mediated immunity will be assess by enumerating antigen-specific Th1 and Th2 cells in Peyer's patch and spleen using cytokine-specific assays and the induction of delayed-type hypersensitivity. The parameters involving the vector and host immunity which affect the magnitude, duration and isotype distribution in serum and secretions of antibodies to the expressed foreign virulence antigen will also be investigated. These include the effect of plasmid copy number, preexisting immunity to the carrier strain, and the presence of the Salmonella virulence plasmid in the carrier strain. Finally, the Salmonella delivery system will be compared with systemic immunization, and oral immunization with the antigen coupled to an oral adjuvant (CTB), for magnitude, duration and isotype distribution. These studies will provide valuable information on the potential utility of the Salmonella delivery system for the induction of immunity to the cloned P. gingivalis HagB and should increase our understanding of the immune system and provide information that will be useful in designing vaccine strategies.
| Pathangey, Latha; Kohler, James J; Isoda, Ryutaro et al. (2009) Effect of expression level on immune responses to recombinant oral Salmonella enterica serovar Typhimurium vaccines. Vaccine 27:2707-11 |
