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抗原 Sm-p80:使用 TLR4 激动剂疫苗佐剂葡糖基脂质 A-明矾在小鼠和非人灵长类动物模型中的预防功效。

antigen Sm-p80: prophylactic efficacy using TLR4 agonist vaccine adjuvant glucopyranosyl lipid A-Alum in murine and non-human primate models.

机构信息

Center for Tropical Medicine and Infectious Diseases, Texas Tech University Health Sciences Center, Lubbock, Texas, USA.

Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas, USA.

出版信息

J Investig Med. 2018 Dec;66(8):1124-1132. doi: 10.1136/jim-2018-000786. Epub 2018 Jul 10.

Abstract

Sm-p80, the large subunit of calpain, is a leading candidate for a schistosomiasis vaccine. The prophylactic and antifecundity efficacy of Sm-p80 has been tested in three animal models (mouse, hamster and baboon) using a multitude of vaccine formulations and approaches. In our continual effort to enhance the vaccine efficacy, in this study, we have utilized the adjuvant, synthetic hexa-acylated lipid A derivative, glucopyranosyl lipid A (GLA) formulated in aluminum (GLA-Alum) with recombinant Sm-p80. The rSm-p80+GLA-Alum immunization regimen provided 33.33%-53.13% reduction in worm burden in the mouse model and 38% worm burden reduction in vaccinated baboons. Robust Sm-p80-specific immunoglobulin (Ig)G, IgG1, IgG2a and IgM responses were observed in all immunized animals. The rSm-p80+GLA-Alum coadministration induced a mix of T-helper (Th) cells (Th1, Th2 and Th17) responses as determined via the release of interleukin (IL)-2, IL-4, IL-18, IL-21, IL-22 and interferon-γ.

摘要

Sm-p80 是钙蛋白酶的大亚基,是血吸虫病疫苗的主要候选者。Sm-p80 的预防性和抗生育功效已在三种动物模型(小鼠、仓鼠和狒狒)中使用多种疫苗制剂和方法进行了测试。为了提高疫苗的疗效,在这项研究中,我们使用了佐剂、合成六酰化脂 A 衍生物葡糖基脂质 A(GLA)与重组 Sm-p80 一起用铝(GLA-Alum)配制。rSm-p80+GLA-Alum 免疫方案使小鼠模型中的虫荷减少了 33.33%-53.13%,接种疫苗的狒狒中的虫荷减少了 38%。所有免疫动物均观察到强烈的 Sm-p80 特异性免疫球蛋白(Ig)G、IgG1、IgG2a 和 IgM 反应。rSm-p80+GLA-Alum 共同给药诱导了辅助性 T 细胞(Th)细胞(Th1、Th2 和 Th17)反应的混合,这是通过释放白细胞介素(IL)-2、IL-4、IL-18、IL-21、IL-22 和干扰素-γ来确定的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db9e/6288690/f056ba272012/jim-2018-000786f01.jpg

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