Laboratório de Imunologia de Doenças Infecciosas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil; Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais (INCT-DT), Conselho Nacional de Desenvolvimento Científico e Tecnológico, Ministério de Ciência Tecnologia e Inovação Salvador, Bahia, Brazil.
Center of Nanoscience, Nanotechnology and Innovation - CeNano2I, Department of Metallurgical and Materials Engineering, Federal University of Minas Gerais, Brazil.
J Control Release. 2018 Apr 10;275:40-52. doi: 10.1016/j.jconrel.2018.02.004. Epub 2018 Feb 8.
Schistosomiasis is an important parasitic disease affecting >207 million people in 76 countries around the world and causing approximately 250,000 deaths per year. At present, the main strategy adopted for the control of schistosomiasis is the use of safe chemotherapy, such as praziquantel. However, the high rates of reinfection after treatment restrict the use of this treatment approach and assume the need for other forms of control such as vaccination. Sm29 is a protein that is localized in the Schistosoma mansoni tegument of adult worms and schistosomula and is considered a powerful vaccine candidate. Because of the chemical, physical and immunological characteristics of nanoparticles, nanocarriers have received increasing attention. In the field of nanotechnology, gold nanorods are considered potential vaccine carriers. In this study, we bound S. mansoni rSm29 protein to gold nanorods either directly or by cysteamine functionalization. When the worm burden was evaluated, the AuNRs-NH-rSm29 group of immunized mice showed the best protection level (34%). Following AuNRs-NH-rSm29 immunization, we observed a Th1 immunological response in mice with higher production of IFN-γ, mainly by CD4 and CD8 T cells. Furthermore, AuNRs-NH-rSm29 could activate dendritic cells in vitro, enhancing MHCII and MHCI expression and the production of IL-1β in a NLRP3-, ASC- and Caspase-1-dependent manner. In summary, our findings support the use of nanorods as an immunization strategy in vaccine development against infectious diseases.
血吸虫病是一种重要的寄生虫病，影响全球 76 个国家的 2.07 亿多人，每年导致约 25 万人死亡。目前，控制血吸虫病的主要策略是使用安全的化学疗法，如吡喹酮。然而，治疗后的高再感染率限制了这种治疗方法的使用，并假设需要其他形式的控制，如疫苗接种。Sm29 是一种定位于曼氏血吸虫成虫和尾蚴表皮的蛋白质，被认为是一种强有力的疫苗候选物。由于纳米粒子的化学、物理和免疫学特性，纳米载体受到了越来越多的关注。在纳米技术领域，金纳米棒被认为是潜在的疫苗载体。在这项研究中，我们将曼氏血吸虫 rSm29 蛋白直接或通过半胱氨酸功能化结合到金纳米棒上。当评估虫荷时，免疫小鼠的 AuNRs-NH-rSm29 组显示出最佳的保护水平（34%）。在 AuNRs-NH-rSm29 免疫后，我们观察到小鼠产生 Th1 免疫应答，IFN-γ产生增加，主要由 CD4 和 CD8 T 细胞产生。此外，AuNRs-NH-rSm29 可以在体外激活树突状细胞，以 NLRP3、ASC 和 Caspase-1 依赖的方式增强 MHCII 和 MHCI 的表达和 IL-1β 的产生。总之，我们的研究结果支持将纳米棒作为一种免疫策略用于开发针对传染病的疫苗。
