3M-052 作为一种佐剂用于基于 PLGA 微球的利什曼原虫重组蛋白疫苗。

3M-052 as an adjuvant for a PLGA microparticle-based Leishmania donovani recombinant protein vaccine.

机构信息

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.

出版信息

J Biomed Mater Res B Appl Biomater. 2018 May;106(4):1587-1594. doi: 10.1002/jbm.b.33965. Epub 2017 Aug 14.

Abstract

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.

摘要

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。

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