Abstract：
Selenium nanoparticles (SeNPs) enhance the immune response as adjuvants, increasing the efficacy of viral vaccines, including those for COVID-19. However, the efficiency of mucosal SeNPs in boosting vaccine-induced protective immunity against tuberculosis remains unclear. Therefore, this study aims to investigate whether the combination of SeNPs with the AH antigen (Ag85A-HspX) can boost respiratory mucosal immunity and thereby enhance the protective effects against tuberculosis. We synthesized SeNPs and assessed their impact on the immune response and protection against Mycobacterium bovis (M. bovis) as a mucosal adjuvant in mice, administered intranasally at a dose of 20 µg. SeNPs outperformed polyinosinic-polycytidylic acid (Poly IC) in stimulating the maturation of bone marrow-derived dendritic cells (BMDCs), which enhanced antigen presentation. SeNPs significantly activated and proliferated tissue-resident memory T cells (TRMs) and effector CD4+ T cells in the lungs. The vaccines elicited specific antibody responses in the respiratory tract and stimulated systemic Th1 and Th17 immune responses. Immunization with AH and SeNPs led to higher levels of mucosal secretory IgA in bronchoalveolar lavage fluid (BALF) and secretory IL-17 in splenocytes. Moreover, SeNPs immunized mice showed reduced M. bovis infection loads and inflammatory lesions in the lungs post-challenge. Notably, immunization with AH and SeNPs significantly reduced bacterial load in the lungs, achieving the lowest levels compared to all other tested groups. This study calls for pre-clinical investigation of AHB-SeNPs as an anti-bovine tuberculosis vaccine and for exploring its human vaccine potential, which is anticipated to aid in the development of innovative vaccines or adjuvants.
摘要：
硒纳米颗粒（SeNPs）作为佐剂增强免疫反应，提高病毒疫苗的功效，包括COVID-19。然而,粘膜SeNPs在增强疫苗诱导的抗结核保护性免疫方面的有效性尚不清楚.因此,本研究旨在探讨SeNPs与AH抗原(Ag85A-HspX)的组合是否可以增强呼吸道粘膜免疫,从而增强对结核病的保护作用.我们合成了SeNPs，并评估了它们对免疫反应和对牛分枝杆菌的保护作用（M.bovis）作为小鼠的粘膜佐剂，以20µg的剂量鼻内给药。在刺激骨髓来源的树突状细胞（BMDC）的成熟方面，SeNPs优于聚肌苷酸-聚胞嘧啶酸（PolyIC），增强了抗原呈递。SeNPs显著激活和增殖肺中的组织驻留记忆T细胞(TRM)和效应CD4+T细胞。该疫苗在呼吸道中引起特异性抗体应答并刺激全身性Th1和Th17免疫应答。AH和SeNPs免疫导致支气管肺泡灌洗液（BALF）中粘膜分泌型IgA和脾细胞中分泌型IL-17的水平较高。此外，SeNPs免疫的小鼠在攻击后肺中显示出降低的牛分枝杆菌感染负荷和炎性病变。值得注意的是,用AH和SeNPs免疫显著减少肺部细菌负荷，与所有其他测试组相比，达到最低水平。这项研究要求对AHB-SeNPs作为抗牛结核病疫苗进行临床前研究，并探索其人类疫苗潜力，预计将有助于创新疫苗或佐剂的开发。
