Effect of preexisting immunity to Salmonella on the immune response to recombinant Salmonella enterica serovar Typhimurium expressing a Porphyromonasgingivalis hemagglutinin

Recombinant Salmonella strains expressing foreign heterologous genes have b een extensively studied as live oral vaccine delivery vectors. We have inve stigated the mucosal and systemic immune responses following oral immunizat ion with a recombinant Salmonella enterica serovar Typhimurium expressing t he hemagglutinin HagB from Porphyromonas gingivalis, a suspected etiologica l agent of adult periodontal disease. We have previously shown a primary mu cosal and systemic response following oral immunization with chi 4072/pDMD1 and recall responses following boosting at 14 weeks after primary immuniza tion. In this study, we examined the effects of earlier boosting as well as the effects of deliberately induced immunity to the Salmonella carrier str ain on subsequent immune responses. Mice boosted at week 7 following immuni zation, a point which corresponded to the peak of the primary response, gen erally showed lower responses than those boosted at week 14. When mice were preimmunized with the Salmonella carrier alone and then immunized with the recombinant strain 7 or 14 weeks later, significant reductions were seen f or serum immunoglobulin G (IgG) antibodies at week 14 and for salivary IgA at week 7, No reductions were seen in serum IgA. or vaginal wash IgA antibo dies. Mice appear to be refractory to boosting with orally administered sal monellae at 7 weeks. Deliberate immunization with the carrier strain did no t appreciably affect recall responses at 14 weeks, with the exception of th e serum IgG responses, nor did it affect colonization of the Peyer's patche s.