Co-encapsulation of SOL components in MP enhanced their protective efficacy. One of the most interesting observations in this study was the levels
of IgG and IgA antibodies in the lungs after challenge. The levels of both PTd specific IgA and IgG in the MP group were significantly higher than all other groups ( Fig. 6). The levels of MCP-1 in the lung homogenates were higher in both SOL and MP group in comparison to Quadracel® or AQ formulations at day 3 after challenge (Fig. 7A). After 7 days we detected twice the amount of MCP-1 in the MP group compared to the SOL group. Hence the persistence of MCP-1 was extended after challenge in the MP group. Analysis of TNF-α, IL-10, IFN-γ and IL-12p40 cytokines showed that immunization with MP induced a predominantly Th1-type response in the lungs (Fig. 7B–E). DAPT chemical structure Quadracel® produced a predominantly Th2-type of response. The levels of IL-10 were lower in all groups other
than Quadracel® but surprisingly the levels rebounded to that of Quadracel® at day 7 in SOL. Furthermore, IL-17 levels in lungs from Quadracel® and MP immunized mice were significantly higher than AQ or SOL groups (Fig. 7F). We conclude that immunization with MP induced higher levels of Th1 and Th17 type cytokines, while immunization with Quadracel® induced more Th2 type cytokines. In this study we found that a single subcutaneous immunization with MPs co-encapsulating CpG ODN, IDR and PCEP along with PTd provided better protection against pertussis than these components given in soluble formulation. The co-encapsulation of LY2157299 manufacturer the adjuvants and the antigen in MP provided a significantly higher Th1 and Th17 type response in the lung in spite of lower systemic humoral responses. Multi-component
vaccine formulations require an effective delivery system for co-delivery of all components to the immune cells and tissues to generate a desired response. As such, in the present work we used the polyphosphazene adjuvant PCEP in combination with complexes of CpG ODN and IDR for delivering PTd as a model antigen against pertussis. The formulation was delivered in two ways, either as a Idoxuridine soluble ad-mixture of all the components (SOL) or co-delivered in MPs in which PCEP itself was used as an encapsulating agent without the need for additional component for encapsulation. Here, we found that the MP group had about 100 times lower bacterial burden in the lungs compared to non-immunized mice. The advantage of using MP as a tool is that particulate delivery increases vaccine stability and uptake of the antigen to the MHC class I and class II compartments resulting in induction of both cell-mediated and humoral immune responses [20]. Historically, poly(lactic-co-glycolic acid) (PLGA), MPs and/or nanoparticles have been investigated extensively as delivery systems.