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树状聚合物候选疫苗肽在国内猪中诱导对古典猪瘟病毒的部分保护作用。

Partial protection against classical swine fever virus elicited by dendrimeric vaccine-candidate peptides in domestic pigs.

机构信息

Centre de Recerca en Sanitat Animal, IRTA-UAB, Campus de UAB, 08193 Bellaterra, Barcelona, Spain.

出版信息

Vaccine. 2011 Jun 10;29(26):4422-9. doi: 10.1016/j.vaccine.2011.03.095. Epub 2011 Apr 13.

Abstract

We report the immunogenicity of three dendrimeric peptide vaccine candidates for classical swine fever virus (CSFV). Each dendrimeric construct contained four copies of a B-cell epitope from the E2 glycoprotein of CSFV [construct 1: E2 (694-712); 2: E2 (712-727); 3: E2 (829-842)] joined to a T-cell epitope from the NS3 protein (residues 1446-1460). Intramuscular immunization of domestic pigs with the different constructs significantly reduced the clinical score after lethal challenge with CSFV. In contrast, control pigs developed severe clinical signs of the disease. All pigs vaccinated with construct 1, containing a B-cell epitope from the E2 B-C domain, developed an antibody response that recognized not only the original dendrimeric immunogen but also its constituting E2 epitope in linear form, albeit no neutralizing antibodies were detected prior to viral challenge. Two of these pigs were partially protected, which associated with the induction of IFN-γ producing cells and of neutralizing antibodies upon challenge. Interestingly, the serological response elicited by construct 1 lacked antibodies to E2 A domain, used as infection markers. The dendrimeric approach could therefore provide a basis for the development of CSFV marker (DIVA) vaccines, and contribute to a better understanding of the immune responses against CSFV.

摘要

我们报告了三种树状肽疫苗候选物针对经典猪瘟病毒(CSFV)的免疫原性。每个树状结构都包含 CSFV E2 糖蛋白的四个 B 细胞表位[构建体 1:E2(694-712);2:E2(712-727);3:E2(829-842)],连接到 NS3 蛋白的一个 T 细胞表位(残基 1446-1460)。用不同的构建体肌肉内免疫家猪,可显著降低 CSFV 致死性攻毒后的临床评分。相比之下,对照猪出现严重的疾病临床症状。用包含 E2 B-C 结构域的 B 细胞表位的构建体 1 免疫的所有猪都产生了抗体反应,不仅能识别原始的树状免疫原,还能识别其线性形式的组成 E2 表位,尽管在病毒攻毒前未检测到中和抗体。其中两只猪得到了部分保护,这与 IFN-γ产生细胞的诱导以及攻毒后的中和抗体有关。有趣的是,构建体 1 引起的血清反应缺乏作为感染标志物的 E2 A 结构域的抗体。因此,树状方法可以为 CSFV 标记(DIVA)疫苗的开发提供基础,并有助于更好地了解针对 CSFV 的免疫反应。

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