Department of Laboratory Sciences, School of Allied Medical Sciences, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Antimicrobial Resistance Research Center, Department of Medical Bacteriology and Virology, Qaem University Hospital, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Microb Pathog. 2021 May;154:104842. doi: 10.1016/j.micpath.2021.104842. Epub 2021 Mar 21.
Tuberculosis (TB), caused by Mycobacterium tuberculosis (M. tuberculosis), is one of the most common and dangerous infectious diseases in the world. Despite vaccination with BCG, it is still considered as a major health problem. Therefore, design and production of an effective novel vaccine against TB is necessary. Our aim was to evaluate immunogenicity of HspX/EsxS fusion protein of M. tuberculosis along with ISCOMATRIX, PLUSCOM nano-adjuvants and MPLA through the subcutaneous route in mice model.
HspX/EsxS fused protein of M. tuberculosis was cloned, expressed and purified in the prokaryotic system. ISCOMATRIX and PLUSCOM nano-adjuvants were prepared by film hydration method. Subcutaneous immunization of BALB/c mice was performed by different formulations. IFN-γ, IL-4, IL-17 and TGF-β cytokines levels as well as serum IgG1, IgG2a.
Our results showed that subcutaneous administration of mice with HspX/EsxS along with three adjuvants, ISCOMATRIX, PLUSCOM and MPLA increased immunogenicity of multi-stage fusion protein of M. tuberculosis. Additionally, HspX/EsxS protein + ISCOMATRIX or + PLUSCOM nano-adjuvants induced stronger Th1, IgG2a and IgG1 immune responses compared to MPLA adjuvant. Totally, HspX/EsxS/ISCOMATRIX/MPLA, HspX/EsxS/PLUSCOM/MPLA and two BCG booster groups could significantly induce higher Th1 and IgG2a immune responses.
With regard to ability of ISCOMATRIX, PLUSCOM and MPLA adjuvants to increase immunogenicity of HspX/EsxS protein through induction of IFN-γ and IgG2a immune responses, it seems that these adjuvants and especially ISCOMATRIX and PLUSCOM, could also improve BCG efficacy as a BCG booster.
结核病（TB）是由结核分枝杆菌（M. tuberculosis）引起的，是世界上最常见和最危险的传染病之一。尽管接种了卡介苗（BCG），但它仍然是一个主要的健康问题。因此，设计和生产针对结核病的新型有效疫苗是必要的。我们的目的是评估结核分枝杆菌 HspX/EsxS 融合蛋白与 ISCOMATRIX、PLUSCOM 纳米佐剂和 MPLA 联合通过皮下途径在小鼠模型中的免疫原性。
结核分枝杆菌 HspX/EsxS 融合蛋白在原核系统中进行克隆、表达和纯化。ISCOMATRIX 和 PLUSCOM 纳米佐剂通过薄膜水化法制备。通过不同的配方对 BALB/c 小鼠进行皮下免疫接种。IFN-γ、IL-4、IL-17 和 TGF-β细胞因子水平以及血清 IgG1、IgG2a。
我们的结果表明，在三种佐剂（ISCOMATRIX、PLUSCOM 和 MPLA）的共同作用下，皮下给予 HspX/EsxS 融合蛋白可增强结核分枝杆菌多阶段融合蛋白的免疫原性。此外，与 MPLA 佐剂相比，HspX/EsxS 蛋白+ISCOMATRIX 或+PLUSCOM 纳米佐剂诱导更强的 Th1、IgG2a 和 IgG1 免疫反应。总的来说，HspX/EsxS/ISCOMATRIX/MPLA、HspX/EsxS/PLUSCOM/MPLA 和两个 BCG 增强组可显著诱导更高的 Th1 和 IgG2a 免疫反应。
鉴于 ISCOMATRIX、PLUSCOM 和 MPLA 佐剂通过诱导 IFN-γ和 IgG2a 免疫反应来增强 HspX/EsxS 蛋白的免疫原性，这些佐剂，尤其是 ISCOMATRIX 和 PLUSCOM，也可能增强 BCG 作为 BCG 增强剂的效果。
