Immunogenicity of IpaC-Hybrid Proteins Expressed in the Shigella flexneri 2a Vaccine Candidate SC602

We have investigated the capacity of live attenuated Shigella flexneri strains to act as vectors for the induction of local and systemic antibody responses against heterologous epitopes. The S. flexneri IpaC antigen was selected as a carrier protein into which the C3 neutralizing epitope of the poliovirus VP1 protein was inserted in eight sites distributed along IpaC. The resulting IpaC-C3 hybrid proteins were expressed from recombinant plasmids in the S. flexneri 2a vaccine candidate, SC602. Their production was similar to that of wild-type IpaC. All of the hybrid proteins but one were secreted as efficiently as wild-type IpaC. Immunization of mice with each of the recombinant SC602 derivatives reveals that one construct is able to induce serum and local anti-C3 antibodies, showing that at least one permissive site of insertion within IpaC can be defined. Furthermore, mouse-to-mouse variability in the anti-C3 response indicates that the amount of hybrid proteins produced in the host by SC602 should be improved for optimal use of S. flexneri live attenuated strains as mucosal vectors for foreign epitopes.