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壳聚糖制剂可提高基于促性腺激素释放激素I肽的疫苗的免疫原性。

Chitosan formulations improve the immunogenicity of a GnRH-I peptide-based vaccine.

作者信息

Sáenz Leonardo, Neira-Carrillo Andrónico, Paredes Rodolfo, Cortés Marlies, Bucarey Sergio, Arias José L

机构信息

Veterinary Biotechnological Center (BIOVETEC), Chile.

出版信息

Int J Pharm. 2009 Mar 18;369(1-2):64-71. doi: 10.1016/j.ijpharm.2008.10.033. Epub 2008 Nov 12.

Abstract

Peptide vaccines using specific antigens with poor immunogenicity like GnRH-I are unable to develop an effective adaptive immune response and require the presence of adjuvants, essential to lymphocytic activation. Three chitosan formulations were evaluated for their ability as adjuvant of a poor immunogenic peptide vaccine against GnRH-I. Male Sprague-Dawley rats were immunized subcutaneously with recombinant His-GnRH-tandem-repeat peptide in high, low and phosphorylated high molecular weight chitosan solution at 0.5% (w/v). Freund's complete adjuvant was used as a positive control of immune response. Our results suggest that different chitosan formulations as adjuvant, with high or low viscosity degree allow inducing a high and persistent immune response against a poor immunogenic recombinant peptide. We found that the immune response was mediated by a increasing of IgG isotype 1, which were significantly greater than levels presented by the animals immunized with Freund's complete adjuvant. Nevertheless, chitosan with low molecular weight and highest acetylation degree was able to induce an immune response mediated by IgG isotype 2a. Additionally, high molecular weight phosphorylated chitosan, in which the phosphate groups were linked to N-acetyl-d-glucosamine unit, the immune response was reduced. All the immune responses obtained with chitosan as adjuvant were able to neutralize effectively the GnRH hormone proves by reducing of animal steroidogenesis and spermatogenesis demonstrating its capacity to improve immunogenicity in peptide vaccine.

摘要

使用免疫原性较差的特定抗原(如促性腺激素释放激素-I,GnRH-I)的肽疫苗无法产生有效的适应性免疫反应,需要佐剂的存在,而佐剂对淋巴细胞激活至关重要。评估了三种壳聚糖制剂作为针对GnRH-I的低免疫原性肽疫苗佐剂的能力。将雄性Sprague-Dawley大鼠皮下注射重组His-GnRH串联重复肽,分别置于0.5%(w/v)的高、低和磷酸化高分子量壳聚糖溶液中。弗氏完全佐剂用作免疫反应的阳性对照。我们的结果表明,不同粘度程度的壳聚糖制剂作为佐剂,能够诱导针对低免疫原性重组肽产生强烈且持久的免疫反应。我们发现免疫反应是由IgG 1型的增加介导的,其水平显著高于用弗氏完全佐剂免疫的动物。然而,低分子量和最高乙酰化程度的壳聚糖能够诱导由IgG 2a型介导的免疫反应。此外,磷酸基团连接到N-乙酰-d-葡萄糖胺单元的高分子量磷酸化壳聚糖,免疫反应降低。以壳聚糖作为佐剂获得的所有免疫反应都能够通过降低动物的类固醇生成和精子发生有效地中和GnRH激素,证明其在肽疫苗中提高免疫原性的能力。

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