Carnauba wax nanoparticles enhance strong systemic and mucosal cellular and humoral immune responses to HIV-gp140 antigen.

Carnauba wax nanoparticles enhance strong systemic and mucosal cellular and humoral immune responses to HIV-gp140 antigen.
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DOI:
10.1016/j.vaccine.2010.11.084
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发表时间:
2011-02-01
期刊:
影响因子:
5.5
通讯作者:
Shattock, Robin
Shattock, Robin
中科院分区:
医学3区
文献类型:
--
作者:
Arias, Mauricio A.;Loxley, Andrew;Eatmon, Christy;Van Roey, Griet;Fairhurst, David;Mitchnick, Mark;Dash, Philip;Cole, Tom;Wegmann, Frank;Sattentau, Quentin;Shattock, Robin

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在没有炎症的粘膜间隔诱导对HIV的体液反应对于疫苗设计是重要的。我们开发了带电荷的蜡纳米颗粒,它能有效地吸附蛋白质抗原,并在没有炎症的情况下被DC内化。吸附了HIV-gp140的纳米颗粒在体外比单独抗原诱导更强的T细胞增殖反应。当抗原与TLR配体共吸附时,这种反应大大增强。对小鼠的免疫原性研究表明,用HIV-gp140抗原吸附纳米粒皮内接种可诱导高水平的特异性免疫球蛋白。重要的是,鼻腔免疫HIV-gp140吸附纳米颗粒大大增强了血清和阴道的免疫球蛋白和免疫球蛋白A反应。我们的结果表明,携带HIV-gp140的蜡纳米粒可以诱导强大的细胞/体液免疫反应,而不会产生炎症,可能成为HIV疫苗候选的有效粘膜佐剂。
Induction of humoral responses to HIV at mucosal compartments without inflammation is important for vaccine design. We developed charged wax nanoparticles that efficiently adsorb protein antigens and are internalized by DC in the absence of inflammation. HIV-gp140-adsorbed nanoparticles induced stronger in vitro T-cell proliferation responses than antigen alone. Such responses were greatly enhanced when antigen was co-adsorbed with TLR ligands. Immunogenicity studies in mice showed that intradermal vaccination with HIV-gp140 antigen-adsorbed nanoparticles induced high levels of specific IgG. Importantly, intranasal immunization with HIV-gp140-adsorbed nanoparticles greatly enhanced serum and vaginal IgG and IgA responses. Our results show that HIV-gp140-carrying wax nanoparticles can induce strong cellular/humoral immune responses without inflammation and may be of potential use as effective mucosal adjuvants for HIV vaccine candidates.
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