Development of safe oral vaccines based on Lactobacillus as a vector with adjuvanticity

Single dose live oral vaccines are most urgently needed to meet the prerequisites as phrased in the `Children's Vaccine Initiative'. The use of a Generally Regarded as Safe (GRAS) micro-organism as Lactobacillus as oral vaccine carrier has the advantage a.o. that these bacteria have probiotic, health beneficial properties and can be used as `food-grade' delivery vehicles. In mice, using model antigens we have investigated the properties of various Lactobacillus strains as a carrier and as an adjuvant. It was shown that some Lactobacillus-strains do possess adjuvant properties to a level as observed with well established water-in-oil adjuvants whereas other strains do not provide immuno-enhancing effects. Haptenated Lactobacillus demonstrated the carrier function which is provided in serum antibody as well as DTH responses. Synthetic peptides with at least one B-cell and one T-cell epitope coupled to the surface of the bacteriae indicated that surface expression best supports immune response induction (antibodies, DTH). Expression vectors for Lactobacillus with surface anchored viral- and bacterial peptide-antigens as well as vectors allowing the intracellular expression and secretion of antigens have been developed and are being tested in vaccine feasibility studies.