Evaluation of the Delivery Modes and Their Effects on the Antigenicity Properties of a Synthetic Multivalent Mycobacterial Gene in Mice

An ubiquitin conjugated multivalent mycobacterial gene vacIII (containing seven immunogenic mycobacterial epitopes or genes; esat-6 (P1), esat-6 (P2), phos1 (65-83), phos1 (129-137), phos1 (166-175), hsp 16.3 and mtb 8.4) was developed and packaged in different modes of antigen delivery systems including 1) DNA vaccination (pVaxVacIII), 2) oral vaccine strain Salmonella typhi Ty21a as a delivery vehicle for the DNA vaccine (StV3dvc) and 3) a recombinant S. typhi Ty21a (StV3) expressing the VacIII antigen on its surface using a synthetic version of the ice-nucleation protein (Inp) of Pseudomonas syringae. Immunization of C57BL/6 mice with pVaxVacIII elicited both humoral and cell-mediated responses although the overall effect tended to polarize towards the Th1 response (high IFN-γ and low IL-4). StV3dvc and StV3 (both of which were delivered orally) on the other hand triggered an immune response which polarized towards Th2. Thus the bacteria S. typhi Ty21a was able to modulate the immunological properties of the DNA vaccine candidate. In conclusion, the different delivery models altered the antigenicity properties of the synthetic multivalent mycobacterial gene. However, the level of immunity induced by different delivery models may be insufficient for protection against Mycobacterium infection.