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新型微颗粒寨卡疫苗经肌肉注射后,在临床前小鼠模型中诱导出显著的免疫应答。

Novel microparticulate Zika vaccine induces a significant immune response in a preclinical murine model after intramuscular administration.

机构信息

Vaccine Nanotechnology Laboratory, Center for Drug Delivery Research, College of Pharmacy, Mercer University, Atlanta, GA 30341, United States.

Vaccine Nanotechnology Laboratory, Center for Drug Delivery Research, College of Pharmacy, Mercer University, Atlanta, GA 30341, United States.

出版信息

Int J Pharm. 2022 Aug 25;624:121975. doi: 10.1016/j.ijpharm.2022.121975. Epub 2022 Jul 3.

Abstract

Despite the detrimental effects associated with Zika infection, there are no approved treatments or vaccines available. To address the need for a safe and effective vaccine for Zika, we formulated poly(lactic-co-glycolic) acid (PLGA) polymeric vaccine microparticles (MP) encapsulating the inactivated Zika virus, along with adjuvant MP encapsulating Alhydrogel® and MPL-A®. We characterized the vaccine MP for size, surface charge, morphology, encapsulation efficiency, and antigen integrity. Further, we evaluated immunogenicity and cytotoxicity of vaccine MP in vitro in murine dendritic cells. Vaccine MP with adjuvants induced significantly higher production of nitric oxide, a marker of innate immunity, when compared to the untreated cells. In addition, vaccine MP with or without adjuvants induced increased autophagy in murine dendritic cells when compared to inactivated Zika virus, which is critical in antigen presentation. Next, we evaluated in vivo efficacy of vaccine MP with and without adjuvants in a preclinical murine model by measuring the immune response after intramuscular administration. Vaccine MP with adjuvants induced significant IgG, Ig2a, and IgG1 titers as compared to the control group of untreated mice. Thus, this study provided the 'proof-of-concept' for a microparticulate Zika vaccine.

摘要

尽管寨卡病毒感染会带来有害影响,但目前尚无获得批准的治疗方法或疫苗。为了解决寨卡病毒的安全有效疫苗的需求,我们制备了聚(乳酸-共-乙醇酸)(PLGA)聚合物疫苗微球(MP),包封了灭活的寨卡病毒,以及包封 Alhydrogel®和 MPL-A®的佐剂 MP。我们对疫苗 MP 的粒径、表面电荷、形态、包封效率和抗原完整性进行了表征。此外,我们还在体外评估了疫苗 MP 在小鼠树突状细胞中的免疫原性和细胞毒性。与未处理的细胞相比,含有佐剂的疫苗 MP 可显著提高一氧化氮(先天免疫的标志物)的产生。此外,与灭活的寨卡病毒相比,含有或不含有佐剂的疫苗 MP 可诱导小鼠树突状细胞中的自噬增加,这在抗原呈递中至关重要。接下来,我们通过测量肌肉内给药后的免疫反应,在临床前小鼠模型中评估了含佐剂和不含佐剂的疫苗 MP 的体内疗效。与未处理的对照小鼠相比,含有佐剂的疫苗 MP 可诱导显著更高的 IgG、Ig2a 和 IgG1 滴度。因此,这项研究为寨卡病毒微粒疫苗提供了“概念验证”。

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