中文摘要：研究分析了TOLL样受体（TLR）7/8促进剂3M-052与杜氏利什曼虫36-kDa核苷水解酶重组蛋白抗原（NH36）联合使用时的佐剂特性。将NH36、3M-052分配包被于PLGA微胶囊（MPs）中，其装载效率分别为83%和95%。体外试验表明，MP包被的NH36和3M-052能够激发机体产生更高滴度的T(H)1相关的IgG2a 和 IgG2b抗体浓度，且诱导脾细胞产生IFN的效率最高。这些结果表明，PLGA 微纳米颗粒装载的3M-052能够作为佐剂用于制备杜氏利什曼虫疫苗。
外文摘要：It is believed that an effective vaccine against leishmaniasis will require a T helper type 1 (T(H)1) immune response. In this study, we investigated the adjuvanticity of the Toll-like receptor (TLR) 7/8 agonist 3M-052 in combination with the Leishmania donovani 36-kDa nucleoside hydrolase recombinant protein antigen (NH36). NH36 and 3M-052 were encapsulated in separate batches of poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs). The loading efficiency for NH36 was 83% and for 3M-052 was above 95%. In vitro stimulation of bone marrow-derived dendritic cells, measured by IL-12 secretion, demonstrated that 3M-052 (free or MP-formulated) had a concentration-dependent immunostimulatory effect with an optimum concentration of 2 mu g/mL. In immunogenicity studies in BALB/c mice, MP-formulated NH36 and 3M-052 elicited the highest serum titers of T(H)1-associated IgG2a and IgG2b antibodies and the highest frequency of IFN-producing splenocytes. No dose dependency was observed among MP/NH36/3M-052 groups over a dose range of 4-60 mu g 3M-052 per injection. The ability of MP-formulated NH36 and 3M-052 to elicit a T(H)1-biased immune response indicates the potential for PLGA MP-formulated 3M-052 to be used as an adjuvant for leishmaniasis vaccines.
外文关键词：immune response, microparticle, poly(lactic-co-glycolic acid), vaccine
作者：Wang, Q; Barry, MA; Seid, CA; Hudspeth, EM; McAtee, CP; Heffernan, MJ
作者单位：美国休斯敦贝勒医学院
期刊名称：JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS
期刊影响因子：3.189
出版年份：2018
出版刊次：5
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