Kumar Sunny, Kesharwani Siddharth S, Kuppast Bhimanna, Bakkari Mohammed Ali, Tummala Hemachand
Department of Pharmaceutical Sciences, College of Pharmacy & Allied Health Professions, South Dakota State University, SAV # 255, Box 2202C, Brookings, SD 57007, USA.
Department of Pharmaceutical Sciences, College of Pharmacy & Allied Health Professions, South Dakota State University, SAV # 255, Box 2202C, Brookings, SD 57007, USA; Chicago College of Pharmacy, 555, 31st Street, Downers Grove, IL 60515, USA.
J Control Release. 2017 Sep 10;261:263-274. doi: 10.1016/j.jconrel.2017.06.026. Epub 2017 Jun 29.
New and improved vaccines are needed against challenging diseases such as malaria, tuberculosis, Ebola, influenza, AIDS, and cancer. The majority of existing vaccine adjuvants lack the ability to significantly stimulate the cellular immune response, which is required to prevent the aforementioned diseases. This study designed a novel particulate based pathogen-mimicking vaccine delivery system (PMVDS) to target antigen-presenting-cells (APCs) such as dendritic cells. The uniqueness of PMVDS is that the polymer used to prepare the delivery system, Inulin Acetate (InAc), activates the innate immune system. InAc was synthesized from the plant polysaccharide, inulin. PMVDS provided improved and persistent antigen delivery to APCs as an efficient vaccine delivery system, and simultaneously, activated Toll-Like Receptor-4 (TLR-4) on APCs to release chemokine's/cytokines as an immune-adjuvant. Through this dual mechanism, PMVDS robustly stimulated both the humoral (>32 times of IgG1 levels vs alum) and the cell-mediated immune responses against the encapsulated antigen (ovalbumin) in mice. More importantly, PMVDS stimulated both cytotoxic T cells and natural killer cells of cell-mediated immunity to provide tumor (B16-ova-Melanoma) protection in around 40% of vaccinated mice and significantly delayed tumor progression in rest of the mice. PMVDS is a unique bio-active vaccine delivery technology with broader applications for vaccines against cancer and several intracellular pathogens, where both humoral and cellular immune responses are desired.
需要研发针对疟疾、结核病、埃博拉病毒、流感、艾滋病和癌症等具有挑战性疾病的新型改良疫苗。大多数现有的疫苗佐剂缺乏显著刺激细胞免疫反应的能力,而这对于预防上述疾病是必需的。本研究设计了一种新型的基于颗粒的病原体模拟疫苗递送系统(PMVDS),以靶向抗原呈递细胞(APC),如树突状细胞。PMVDS的独特之处在于,用于制备递送系统的聚合物醋酸菊粉(InAc)可激活先天免疫系统。InAc由植物多糖菊粉合成。作为一种高效的疫苗递送系统,PMVDS能将抗原更好且持续地递送至APC,同时激活APC上的Toll样受体4(TLR-4)以释放趋化因子/细胞因子作为免疫佐剂。通过这种双重机制,PMVDS有力地刺激了小鼠针对包封抗原(卵清蛋白)的体液免疫反应(IgG1水平是明矾的>32倍)和细胞介导免疫反应。更重要的是,PMVDS刺激了细胞介导免疫的细胞毒性T细胞和自然杀伤细胞,在约40%的接种小鼠中提供了肿瘤(B16-ova-黑色素瘤)保护,并显著延缓了其余小鼠的肿瘤进展。PMVDS是一种独特的生物活性疫苗递送技术,在针对癌症和多种细胞内病原体的疫苗方面具有更广泛的应用,这些疫苗需要同时激发体液免疫和细胞免疫反应。