Lipid nanocapsule as vaccine carriers for his-tagged proteins: evaluation of antigen-specific immune responses to HIV I His-Gag p41 and systemic inflammatory responses.
Lipid nanocapsule as vaccine carriers for his-tagged proteins: evaluation of antigen-specific immune responses to HIV I His-Gag p41 and systemic inflammatory responses.
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DOI：
10.1016/j.ejpb.2011.10.016
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发表时间：
2012-02
期刊：
影响因子：
--
通讯作者：
Mumper RJ
中科院分区：
文献类型：
--
作者：
Wadhwa S;Jain A;Woodward JG;Mumper RJ
本研究的目的是设计新型的表面螯合镍纳米胶囊(Ni-NCS)作为组氨酸(His)标记蛋白抗原的疫苗递送系统。Ni-NCs通过高亲和力的非共价相互作用与His标记的模型蛋白结合。优化后的Ni-NCS的平均直径为214.9 nm，Zeta电位为-14.8 mV。His标记的绿色荧光蛋白(His-GFP)和His标记的HIV-1 Gag p41(His-Gag p41)与Ni-NCS的最佳结合比分别为1：221和1：480w/w。用Ni-NCS处理DC2.4细胞后，细胞活力在24小时内没有明显下降(5%)。以His-Gag p41为模型抗原，进一步评价了Ni-NCS的抗体反应。给BALB/c小鼠在第0天(最好)和第14天(增强)皮下给药，然后在第28天收集血清。与氢氧化铝(AH)佐剂的His-Gag p41(1μg)相比，1和0.5μg剂量的Gag p41-His-Ni-NCS(相当于His-Gag p41)的血清His-Gag p41特异性抗体水平显著升高。GAG p41-His-Ni-NCS(1μg)诱导的小鼠血清IgG2a水平明显高于AH佐剂的His-GAG p41。BALB/c小鼠皮下注射Ni-NCS后，其全身IL-12/p40和CCL5/RANTES炎性细胞因子水平并未升高。综上所述，Ni-NCS可以结合His标记的蛋白质，具有作为抗原递送系统的潜力，能够以比铝佐剂低得多的剂量产生强大的抗原特异性抗体，并且不会引起全身促炎因子IL-12/p40和CCL5/RANTES细胞因子的显著升高。
The purpose of this study was to design novel nanocapsules (NCs) with surface-chelated nickel (Ni-NCs) as a vaccine delivery system for histidine (His)-tagged protein antigens. Ni-NCs were characterized for binding His-tagged model proteins through high affinity non-covalent interactions. The mean diameter and zeta potential of the optimized Ni-NCs was 214.9 nm and - 14.8 mV, respectively. The optimal binding ratio of His-tagged Green Fluorescent Protein (His-GFP) and His-tagged HIV-1 Gag p41 (His-Gag p41) to the Ni-NCs was 1:221 and 1:480 w/w, respectively. Treatment of DC2.4 cells with Ni-NCs did not result in significant loss in the cell viability up to 24 h (<5%). We further evaluated the antibody response of the Ni-NCs using His-Gag p41 as a model antigen. Formulations were administered subcutaneously to BALB/c mice at day 0 (prime) and 14 (boost) followed by serum collection on day 28. Serum His-Gag p41 specific antibody levels were found to be significantly higher at 1 and 0.5 μg doses of Gag p41-His-Ni-NCs (His-Gag p41 equivalent) compared to His-Gag p41 (1 μg) adjuvanted with aluminum hydroxide (AH). The serum IgG2a levels induced by Gag p41-His-Ni-NCs (1 μg) were significantly higher than AH adjuvanted His-Gag p41. The Ni-NCs alone did not result in elevation of systemic IL-12/p40 and CCL5/RANTES inflammatory cytokine levels upon subcutaneous administration in BALB/c mice. In conclusion, the proposed Ni-NCs can bind His-tagged proteins and have the potential to be used as antigen delivery system capable of generating strong antigen specific antibodies at doses much lower than with aluminum based adjuvant and causing no significant elevation of systemic proinflammatory IL-12/p40 and CCL5/RANTES cytokines.
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DOI：
10.4049/jimmunol.0900164
发表时间：
2009-10-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
McKee AS;Munks MW;MacLeod MK;Fleenor CJ;Van Rooijen N;Kappler JW;Marrack P
通讯作者：
Marrack P
影响因子：
3.7
作者：
Patel, Jigna D.;O'Carra, Ronan;Mumper, Russell J.
通讯作者：
Mumper, Russell J.
DOI：
10.1016/s0021-9673(00)93969-4
发表时间：
1987-12-18
期刊：
JOURNAL OF CHROMATOGRAPHY
影响因子：
--
作者：
HOCHULI, E;DOBELI, H;SCHACHER, A
通讯作者：
SCHACHER, A
影响因子：
5.5
作者：
Aline, Fleur;Brand, Denys;Dimier-Poisson, Isabelle
通讯作者：
Dimier-Poisson, Isabelle
DOI：
10.1111/j.1749-6632.1995.tb44447.x
发表时间：
1995-01-01
期刊：
COMBINED VACCINES AND SIMULTANEOUS ADMINISTRATION
影响因子：
--
作者：
ALVING, CR
通讯作者：
ALVING, CR