Development of Live Bacterial Delivery Systems for Presentation of Dengue EDIII To The Mucosal Immune System

Abstract

Dengue virus (DENV) EDIII protein is a popular subunit vaccine candidate. To develop a non-parenteral vaccine, the use of BPZE1 (attenuated Bordetella pertussis vaccine strain) was investigated. EDIII was fused to the BrkA or PTX virulence factor. Immunising BALB/c mice via the respiratory route with either strain elicited weak EDIII-specific responses and no response against DENV. As an alternative approach, the food-grade bacterium L. lactis was utilised. Recombinant strains producing cytoplasmic, secreted or cell wall-associated EDIII were generated. Immunising C57BL/6 mice via the respiratory route elicited weak EDIII-specific responses. Only a single mouse immunised with the cytoplasmic EDIII construct exhibited some activity against DENV2. Investigation of T cell responses revealed significant IFN-g but not IL-4 production in splenocyte cultures from mice immunised with this construct. Future work includes assessing the protective efficacy of this response, and also investigating the effect of a heterologous prime boost strategy on circulating IgG levels.