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bioRxiv · 10.1101/2022.10.24.513633

Conventional dendritic cells 2, the targeted antigen-presenting-cell, induces enhanced type 1 immune responses in mice immunized with CVC1302 in oil formulation

Du, L.·Qiao, X.·Zhang, Y.·Hou, L.·Yu, X.·Cheng, H.·Chen, J.·Zheng, Q.·Hou, J.·Tong, G.
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Abstract

Multifunctional CD4+ T helper 1 (Th1) cells, producing IFN-{gamma}, TNF- and IL-2, define a correlate of vaccine-mediated protection against intracellular infection. In our previous study, we found that CVC1302 in oil formulation promoted the differentiation of IFN-{gamma}+/TNF-+/IL-2+ Th1 cells. In order to extend the application of CVC1302 in oil formulation, this study aimed to elucidate the mechanism of action in improving the Th1 immune response. Considering the signals required for the differentiation of CD4+ T cells to Th1 cells, we detected the distribution of innate immune cells and the model antigen OVA-FITC in lymph node (LN), as well as the quantity of cytokines produced by the innate immune cells. The results of these experiments show that, cDC2 and OVA-FITC localized to inter-follicular region (IFR) of the draining lymph nodes, inflammatory monocytes localized to both IFR and T cell zone, which mainly infiltrate from the blood. In this inflammatory niche within LN, CD4+ T cells were attracted into IFR by CXCL10, secreting by inflammatory monocytes, then activated by IL-12-secreting cDC2. Above all, CVC1302 in oil formulation, on the one hand, targeted antigen and inflammatory monocyte into the LN IFN in order to attract CD4+ T cells, on the other hand, targeted cDC2 to produce IL-12 in order to promote optimal Th1 differentiation. The new finding will provide a blueprint for application of immunopotentiators in optimal formulations. ImportanceAlong with the development of veterinary immunology, immunopotentiator and delivery system were not simply mixed with antigen, more and more attentions paid on the optimal compatibility in order to induce multifunctional immune responses. As reported, LPS formulated in IFA targeted antigens to the IFR of the LN, and recruited Mo into the IFR, then attracted antigen-specific CD4+ T cells, which differentiated into Th1 cells under the IL-12 produced by DC-SIGN+ DC(1). Herein, we further found that CVC1302 formulated with Marcol 52 induced enhanced Th1 immunity. Combined with our previous finding that CVC1302 in oil formulation induced improved humoral immunity, we concluded that CVC1302 in oil formulation provided multifunctional immunity, not only higher antibody titers to prevent pathogen infection, but also cellular immunity cytokine to prevent viral shedding.

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Du, L., Qiao, X., Zhang, Y., Hou, L., Yu, X., Cheng, H., Chen, J., Zheng, Q., Hou, J., Tong, G.. 2022-10-25. Conventional dendritic cells 2, the targeted antigen-presenting-cell, induces enhanced type 1 immune responses in mice immunized with CVC1302 in oil formulation. https://doi.org/10.1101/2022.10.24.513633

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