Lactococcus lactis as a vector for oral vaccine delivery : the case of enterohemorrhagic Escherichia coli

In the present thesis we describe the utilization of the live vaccine delivery vector, L. lactis for the development of an oral vaccine against EHEC infection. The vaccine is based on the recombinant expression of the EHEC T3SS protein, EspB in L. lactis. The recombinant vaccine strains could successfully induce mucosal and systemic immune responses in mice upon oral immunization. These responses characterized by the presence of EspB-specific IgA antibodies in the feces and total Igs in the serum. Additionally, a mixed Th1/Th2 response was detected in Peyer’s patches and mesenteric lymph nodes. Furthermore, immunized mice showed protection against intestinal colonization by E. coli O157:H7 upon oral challenge. These findings demonstrate, for the first time, the potential of EspB as a candidate for oral vaccination against EHEC as well as the value of L. lactis as a vaccine delivery vector. The development of an oral vaccine based on the “GRAS” vector, L. lactis, can be particularly beneficial to infants and the elderly, which are the high risk groups for the complications of the hemolytic uremic syndrome. Additionally, the present thesis we address the issue of the gastrointestinal survival of L. lactis in pigs. We offer a proof of concept for the feasible use of aluminium hydroxide (bile acid binder) and camostat mesylate (oral trypsin inhibitor) in oral formulations of L. lactis-based vaccines to improve the gastrointestinal survival of the bacterium in pigs. This will particularly allow the validation of L. lactis-based vaccines in porcine models of infection, which are proven more reliable in the case of EHEC infection. Additionally, with consideration to the physiological similarities between pigs and humans, the application of these protectants can be extended to improve the gastrointestinal survival of L. lactis in humans.