Dendritic cells loaded with HIV-1 p24 proteins adsorbed on surfactant-free anionic PLA nanoparticles induce enhanced cellular immune responses against HIV-1 after vaccination
Dendritic cells loaded with HIV-1 p24 proteins adsorbed on surfactant-free anionic PLA nanoparticles induce enhanced cellular immune responses against HIV-1 after vaccination
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DOI：
10.1016/j.vaccine.2009.05.028
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发表时间：
2009-08-20
期刊：
影响因子：
5.5
通讯作者：
Dimier-Poisson, Isabelle
中科院分区：
文献类型：
--
作者：
Aline, Fleur;Brand, Denys;Dimier-Poisson, Isabelle
具有表面吸附抗原的生物可降解纳米颗粒代表了用于靶向广泛的传染病或癌症的疫苗的体内递送的有前景的方法。我们研究了在无表面活性剂的阴离子（D，L-乳酸，PLA）纳米颗粒表面负载疫苗抗原HIV p24蛋白的树突状细胞的可行性。p24蛋白对纳米粒具有很高的亲和性，免疫后纳米粒上的p24蛋白的抗原性和免疫原性得到了很好的保留。p24包被的纳米颗粒被小鼠树突状细胞（DC）有效地摄取，通过增加MHC-I、MHC-II、CD 40、CD 80和CD 86表面表达并分泌IL-12（p70）和IL-4来诱导DC成熟。我们评估了用p24包被的纳米颗粒脉冲的DC在血液和肠道中引起最佳体液和细胞免疫应答的能力。用p24纳米颗粒脉冲的DC诱导高血清和粘膜抗体产生，并引起强烈的全身和局部淋巴细胞增殖反应，与小鼠中的Th 1/Th 2型反应和全身CTL反应相关。因此，负载抗原的PLA纳米颗粒脉冲的DC可以为针对慢性感染性疾病的细胞疗法疫苗接种提供新的递送工具。(C)2009爱思唯尔有限公司保留所有权利。
Biodegradable nanoparticles with surface adsorbed antigens represent a promising method for in vivo delivery of vaccines targeting a wide range of infectious diseases or cancers. We investigated the feasibility of loading dendritic cells with a vaccine antigen, HIV p24 protein, on the surface of surfactant-free anionic (D,L-lactic acid, PLA) nanoparticles. The p24 protein had a high affinity for the nanoparticles and the antigenicity and immunogenicity of the p24 protein on the nanoparticle was well preserved after immunization. p24-coated nanoparticles were efficiently taken up by mouse dendritic cells (DCs), inducing DC maturation by increasing MHC-I, MHC-II, CD40, CD80 and CD86 surface expression and secreting IL-12 (p70) and IL-4. We evaluated the ability of DCs pulsed with p24-coated nanoparticles to elicit an optimal humoral and cellular immune response in the blood and intestine. DCs pulsed with p24-nanoparticles induced high seric and mucosal antibody production and elicited strong systemic and local lymproliferative responses, correlated with a Th1/Th2-type response, and systemic CTL responses in mice. Thus, DCs pulsed with antigen-loaded PLA nanoparticles may provide a novel delivery tool for cell therapy vaccination against chronic infectious diseases. (C) 2009 Elsevier Ltd. All rights reserved.