Biodegradable poly-l-lactide based microparticles as controlled release delivery system for filarial vaccine candidate antigens
Biodegradable poly-l-lactide based microparticles as controlled release delivery system for filarial vaccine candidate antigens
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DOI：
10.1016/j.ejphar.2014.12.004
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发表时间：
2015-01-15
影响因子：
5
通讯作者：
Kaliraj, Perumal
中科院分区：
文献类型：
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作者：
Anugraha, Gandhirajan;Madhumathi, Jayaprakasam;Kaliraj, Perumal
现代重组疫苗的免疫原性低于需要佐剂来增强疫苗效果的常规疫苗。明矾被用作蛋白质疫苗的标准佐剂，以增强几种疾病的免疫反应。然而，与明矾相关的问题是，它需要在特定的时间间隔多次关闭，以达到足够的免疫力水平。目前，研究了聚-L-丙交酯微粒作为单剂量免疫的佐剂性以克服多次免疫，并报道其对几种疾病有效。在这方面，我们通过复乳法将丝虫重组嵌合多价疫苗候选物如TV和FEP吸附到PLA上，并分析PLA包封的微粒的特性，并评价其在小鼠中的免疫应答。与单独的单剂量明矾或蛋白质相比，研究了单剂量PLA包封的蛋白质的功效。在小鼠中，单剂量的PLA包封的抗原如TV和FEP分别引起显著高于单剂量的明矾吸附的TV/FEP（6000/9000）和单剂量的蛋白质TV/PEP（3000/4000）的抗体滴度的50，000和64，000。进一步的PLA包封的抗原诱导更高水平的细胞增殖以及显著（P < 0.0001）水平的细胞因子应答[PLA-TV诱导高水平的IL-4（Th 2）和IFN-γ（Th 1）细胞因子，而PLA-FEP显示高水平的IL-5（Th 2）和IFN-γ（Th 1）]，表明PLA抗原引起的平衡应答。与单剂量的明矾吸附或单独的蛋白质相比，观察到PLA包封的抗原的总体强的体液和细胞应答。(C)2014爱思唯尔有限公司版权所有。
Modern recombinant vaccines are less immunogenic than conventional vaccines which require adjuvants to enhance the effect of a vaccine. Alum is being used as a standard adjuvant for protein based vaccines to augment immune response in several diseases. However, the problem associated with alum is it requires multiple closes at specific time intervals to achieve the adequate level of immunity. Currently the adjuvanticity of Poly-l-lactide microparticles as single dose immunization was explored to overcome multiple immunization and reported to be effective for several diseases. In this regard we adsorbed filarial recombinant chimeric multivalent vaccine candidates such as TV and FEP on to PLA by double emulsion method and analyzed the characterization of PLA encapsulated microparticles and evaluated its immune responses in mice. The efficacy of single dose of PLA encapsulated proteins was investigated in comparison with single dose of alum or protein alone. In mice, single dose of PLA encapsulated antigens such as TV and FEP elicited significantly high antibody titer of 50,000 and 64,000 respectively than single dose of alum adsorbed TV/FEP (6000/9000) and single dose of protein TV/PEP (3000/4000) alone. Further PLA encapsulated antigens induced higher levels of cellular proliferation together with significant (P < 0.0001) levels of cytokine response [PLA-TV induced high levels of IL-4 (Th2) and IFNI-gamma (Th1) cytokines whereas PLA-FEP showed high levels of IL-5(Th2) and IFN-gamma (Th1)] indicating a balanced response elicited by PLA antigens. Overall strong humoral and cellular responses were observed for PLA encapsulated antigens compared with single dose of alum adsorbed or protein alone. (C) 2014 Elsevier B.V. All rights reserved.