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