Platform technology to deliver prophylactic molecules orally: an example using the Class A select agent Yersinia pestis.

Consumed for centuries, lactic acid bacteria are excellent candidates for the development of safe mucosal delivery vehicles for prophylactic and therapeutic molecules. We have recently reported that the immune response to an effective OspA-expressing L. plantarum vaccine for Lyme disease is modulated by the lipid modification of the antigen. In this study, we investigated if this technology can be applied to developing vaccines for other diseases by focusing on the Class A select agent, Yersinia pestis. We used a number of biochemistry and immunology techniques to determine the localization of the immunogen in our delivery vehicle and to evaluate the mucosal as well as the systemic immune response to the immunogen. We found that only LcrV cloned downstream of the signal sequence of B. burgdorferi OspA ((ss)LcrV), but not wildtype LcrV (LcrV), is localized to the desired peptidoglycan layer of the delivery vehicle. In addition, only mice that received L. plantarum expressing (ss)LcrV produced significant titers of IgG antibody as well as IgA in distant mucosal sites such as lungs and vagina. Furthermore, only L. plantarum expressing (ss)LcrV induced significant amounts of pro-inflammatory cytokines TNFα, IL-12, IFNγ and IL-6 as well as anti-inflammatory IL-10 in human peripheral blood mononuclear cells derived dendritic cells, suggesting that the mechanism by which LcrV-expressing L. plantarum stimulates the immune response involves polarization to Th1 mediated immunity with some involvement of Th2. The study reported here proves that this system is a platform technology to develop oral vaccines for multiple diseases.