Mucosal and systemic immunization against tuberculosis by ISCOMATRIX nano adjuvant co-administered with alginate coated chitosan nanoparticles

采用 ISCOMATRIX 纳米佐剂与藻酸盐包覆的壳聚糖纳米颗粒联合给药,实现对结核病的粘膜和全身免疫

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Abstract

OBJECTIVES: BCG vaccine has no longer been appreciated to immunize against tuberculosis, worldwide, so novel appropriate adjuvants have been dedicated to improve immune responses. This study aimed to evaluate the immunomodulatory effects of ISCOMATRIX as an adjuvant to stimulate potent humoral and cellular immune responses of the PPE17 loaded alginate coated nanoparticles through subcutaneous and intranasal vaccination. MATERIALS AND METHODS: Size, polydispersity index, and morphology of the resulting colloidal particles were explored by dynamic light scattering (DLS). The cellular and/or humoral immune stimulation properties of ISCOMATRIX adjuvant were measured by measuring the level of IFNγ, IL-4, IL-17, and TGFβ in spleen cell cultures and IgG1 and IgG2a in serum and sIgA in nasal lavage of immunized mice, respectively. RESULTS: The spherical cage-like particles of ISCOMATRIX adjuvant have optimal size of 59±6 nm appropriate for an immune adjuvant vaccine. ISCOMATRIX induced robust Th1 (IFN-γ) and IL-17 cytokine response also significant IgG2a and IgG1antibodies in both subcutaneous and intranasal routes and elicited mucosal sIgA response when administered intranasally. As a booster for BCG, ISCOMATRIX induced immune responses only in subcutaneous route. CONCLUSION: These findings indicate that ISCOMATRIX is a promising adjuvant with the potential for increasing cellular and humoral immunity both after subcutaneous and intranasal administration.

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