Oral immunization with recombinant Salmonella typhimurium expressing a cloned Porphyromonas gingivalis hemagglutinin: effect of boosting on mucosal, systemic and immunoglobulin G subclass response.

Abstract

Live avirulent Salmonella typhimurium are convenient vaccine vectors for the delivery of recombinant antigens for the induction of mucosal and systemic immunity. The hagB gene encodes a hemagglutinin of Porphyromonas gingivalis, a suspected causal agent in human adult periodontal disease. In previous studies, we have shown that hagB can be expressed in avirulent S. typhimurium and is immunogenic when given orally to mice. In this study, we evaluated recall responses in both serum and mucosal secretions after boosting. In addition, we have examined the immunoglobulin G (IgG) subclass response in serum to both HagB and the Salmonella carrier. Mice were orally immunized with S. typhimurium expressing the hagB gene and then boosted 14 weeks later. Responses were measured through 27 weeks. Both primary and recall IgG and IgA responses were seen in serum to the purified HagB as well as to the Salmonella carrier. Likewise, mucosal primary and recall responses were seen in saliva, fecal extracts and vaginal washes although the kinetics of the responses differed. The anti-HagB response in serum was dominated by IgG2a during the peak of primary response, prior to boosting and during the peak of the recall response. The anti-S. typhimurium response shifted from predominantly IgG3 following primary immunization to IgG2a after boosting. The IgG1 response was minimal against each antigen. This pattern of IgG subclass distribution is consistent with a Th1-type response. These data indicate that avirulent S. typhimurium is capable of delivering a putative virulence factor from P. gingivalis and inducing a primary and recall response in both serum and secretions and provides a means of studying P. gingivalis virulence factors and for the development of a potential vaccine.