Vaccine development has evolved from killed or live attenuated microorganisms to well-defined synthetic vaccines based on individual proteins or peptides. However, peptide antigens are usually poorly immunogenic and sensitive to proteolytic degradation, and thus require conjugation to carrier proteins, and administration with potentially toxic adjuvants. Lactic acid bacteria have become promising vectors to deliver antigens to mucosal tissues. Combining these two research trends, we have developed a novel peptide delivery system by utilising the group A streptococcus (GAS) pilus structure as a carrier for antigenic peptides, and expressing the modified pili on the surface of the non-pathogenic surrogate Lactococcus lactis. Advantages of this new technology, termed PilVax, include increased peptide immunogenicity and stability, higher safety and low production cost.
In this proof-of-concept study, we identified several regions within the backbone pilin FctA (Spy0128) of a serotype M1 strain that can be replaced with the model peptide OVA324-339 without affecting pilus assembly and display on the surface of L. lactis. Intranasal immunisation of mice with the resulting recombinant L. lactis strain produced strong Ova-specific antibody responses in serum and bronchoalveolar fluid. Further modification of the PilVax design has been carried out, in order to improve adjuvanticity and surface antigen display. Oral vaccination as an alternative immunisation route is also being investigated. The PilVax technology provides a novel system for developing peptide vaccines for mucosal delivery.