Surfactant-free anionic PLA nanoparticles coated with HIV-1 p24 protein induced enhanced cellular and humoral immune responses in various animal models
Surfactant-free anionic PLA nanoparticles coated with HIV-1 p24 protein induced enhanced cellular and humoral immune responses in various animal models
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DOI：
10.1016/j.jconrel.2006.02.006
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发表时间：
2006-05-15
影响因子：
10.8
通讯作者：
Verrier, Bernard
中科院分区：
文献类型：
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作者：
Ataman-Onal, Yasemin;Munier, Severine;Verrier, Bernard
用聚(D，L-丙交酯-乙交酯)或聚(D，L-丙交酯)聚合物制备的微球和纳米粒是一种很有前途的体内递送多肽、蛋白质或脱氧核糖核酸抗原的方法。然而，限制这些递送系统潜力的一个主要问题是包埋的抗原的不稳定或降解。携带表面吸附抗原的带电微粒就是为了解决这一问题而发展起来的，似乎更适合于疫苗应用。我们在这里描述了通过透析法获得的完全不含表面活性剂的新型阴离子聚乳酸纳米颗粒，这使得它们更适合在人类身上使用。该递送系统作为疫苗载体的效力在使用HIV-1p24蛋白的各种动物模型中进行了测试。P24包被的聚乳酸纳米粒(p24/PLA)在小鼠、兔和猕猴体内诱导高抗体滴度(>；10(6))。此外，p24/聚乳酸纳米粒在小鼠体内可诱导强烈的CTL反应和Th1偏向的细胞因子(干扰素-γ、IL-2)的释放。当p24蛋白被涂在聚乳酸纳米颗粒的表面时，似乎比用弗氏佐剂佐剂更能产生面向Th1的反应。最重要的是，p24/PLA颗粒诱导Th1反应的能力在猕猴模型中也得到了证实，因为ELISPOT试验可以检测到高水平的产生干扰素-伽马的CD4(+)T细胞和CD8(+)T细胞。这种蛋白质输送系统证实了带电纳米颗粒在疫苗开发领域的潜力。(C)2006爱思唯尔B.V.保留所有权利。
Microparticles and nanoparticles prepared with poly(D,L-lactide-co-glycolide) (PLGA) or poly(D,L-lactide) (PLA) polymers represent a promising method for in vivo delivery of encapsulated peptide, protein or DNA antigens. However, one major issue that limits the potential of these delivery systems is the instability or the degradation of the entrapped antigen. Charged microparticles carrying surface adsorbed antigen were developed to resolve this problem and appear more suitable for vaccine applications. We describe here new anionic PLA nanoparticles obtained by the dialysis method that are absolutely surfactant-free, which makes them more appropriate for use in humans. The potency of this delivery system as a vaccine carrier was tested in various animal models using HIV-1 p24 protein. p24-coated PLA nanoparticles (p24/PLA) induced high antibody titres (> 10(6)) in mice, rabbits and macaques. Moreover, p24/PLA nanoparticles elicited strong CTL responses and a Th1-biased cytokine release (IFN-gamma, IL-2) in mice. p24 protein seemed to generate a more Th1-oriented response when administered coated onto the surface of PLA nanoparticles than adjuvanted with Freund's adjuvant. Most importantly, the ability of p24/PLA particles to induce Th1 responses was also confirmed in the macaque model, since high levels of IFN-gamma-producing CD4(+) T cells and CD8(+) T cells could be detected by the ELISPOT assay. This protein delivery system confirms the potential of charged nanoparticles in the field of vaccine development. (c) 2006 Elsevier B.V. All rights reserved.