Department of Pediatrics (Section of Tropical Medicine), National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas.
Texas Children's Hospital Center for Vaccine Development, Houston, Texas.
J Biomed Mater Res B Appl Biomater. 2018 May;106(4):1587-1594. doi: 10.1002/jbm.b.33965. Epub 2017 Aug 14.
It is believed that an effective vaccine against leishmaniasis will require a T helper type 1 (T 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 µg/mL. In immunogenicity studies in BALB/c mice, MP-formulated NH36 and 3M-052 elicited the highest serum titers of T 1-associated IgG2a and IgG2b antibodies and the highest frequency of IFNγ-producing splenocytes. No dose dependency was observed among MP/NH36/3M-052 groups over a dose range of 4-60 µg 3M-052 per injection. The ability of MP-formulated NH36 and 3M-052 to elicit a T 1-biased immune response indicates the potential for PLGA MP-formulated 3M-052 to be used as an adjuvant for leishmaniasis vaccines. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1587-1594, 2018.
人们相信，一种有效的利什曼病疫苗将需要 T 辅助型 1（T 1）免疫反应。在这项研究中，我们研究了 Toll 样受体（TLR）7/8 激动剂 3M-052 与利什曼原虫 36-kDa 核苷水解酶重组蛋白抗原（NH36）联合使用的佐剂作用。NH36 和 3M-052 被封装在单独批次的聚（乳酸-共-乙醇酸）（PLGA）微球（MP）中。NH36 的负载效率为 83%，3M-052 则高于 95%。通过白细胞介素-12（IL-12）分泌来测量骨髓来源树突状细胞的体外刺激，表明 3M-052（游离或 MP 制剂）具有浓度依赖性的免疫刺激作用，最佳浓度为 2 µg/mL。在 BALB/c 小鼠的免疫原性研究中，MP 制剂化的 NH36 和 3M-052 引发了 T 1 相关 IgG2a 和 IgG2b 抗体的最高血清滴度和 IFNγ 产生的脾细胞的最高频率。在 4-60 µg 3M-052 每注射剂量范围内，MP/NH36/3M-052 组之间没有观察到剂量依赖性。MP 制剂化的 NH36 和 3M-052 引发 T 1 偏向性免疫反应的能力表明 PLGA MP 制剂化的 3M-052 有可能被用作利什曼病疫苗的佐剂。 © 2017 Wiley Periodicals, Inc. J 生物材料研究杂志 B：应用生物材料，106B：1587-1594，2018。
