Vicente Belén, López-Abán Julio, Rojas-Caraballo Jose, del Olmo Esther, Fernández-Soto Pedro, Ramajo-Martín Vicente, Muro Antonio
Parasite and Molecular Immunology Laboratory, Tropical Disease Research Centre, Universidad de Salamanca (IBSAL-CIETUS), Avda. Licenciado Méndez Nieto s/n, 37007 Salamanca, Spain.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Salamanca (IBSAL-CIETUS), Salamanca, Spain.
Exp Parasitol. 2015 Jul;154:134-42. doi: 10.1016/j.exppara.2015.04.022. Epub 2015 Apr 30.
Fatty acid binding proteins (FABP) from Fasciola hepatica have demonstrated immune cross-protection against schistosomes. The present study was conducted to develop a new formulation of the recombinant FABP rFh15 with the synthetic immunomodulator AA0029 in the adjuvant adaptation (ADAD) vaccination system and to evaluate its ability to induce immune response and protection against the challenge with Schistosoma bovis cercariae. Immunization of BALB/c mice showed high levels of TNFα, IFNγ, interleukin (IL)-2, IL-6, and IL-4 in splenocyte supernatant culture and also high levels of serum specific anti-rFh15 IgG, IgG1, IgG2a IgE and IgM antibodies suggesting a mixed Th1/Th2 immune response. Using this approach, high levels of protection against experimental challenge with S. bovis cercariae were observed in the mouse and hamster models. A marked reduction up to 64% in worm burden, as well as in the number of eggs retained in liver (66%) and intestine (77%) and hepatic lesions (42%), was achieved in vaccinated BALB/c mice. Golden hamsters vaccinated and challenged in similar conditions had reductions in recovered worms (83%), liver eggs (90%), intestine eggs (96%), liver lesions (56%) and worm fecundity (48-80%). These data suggest that formulation of rFh15 in the ADAD vaccination system using the AA0029 immunomodulator could be a good option to drive an effective immunological response against schistosomiasis.
肝片吸虫的脂肪酸结合蛋白(FABP)已显示出对血吸虫的免疫交叉保护作用。本研究旨在开发一种重组FABP rFh15与合成免疫调节剂AA0029在佐剂适应性(ADAD)疫苗接种系统中的新配方,并评估其诱导免疫反应以及抵御牛血吸虫尾蚴攻击的能力。对BALB/c小鼠进行免疫接种后,脾细胞上清液培养物中TNFα、IFNγ、白细胞介素(IL)-2、IL-6和IL-4水平较高,血清特异性抗rFh15 IgG、IgG1、IgG2a、IgE和IgM抗体水平也较高,表明产生了混合的Th1/Th2免疫反应。采用这种方法,在小鼠和仓鼠模型中观察到对牛血吸虫尾蚴实验性攻击具有高水平的保护作用。接种疫苗的BALB/c小鼠的虫体负荷显著降低了64%,肝脏(66%)和肠道(77%)中保留的虫卵数量以及肝脏病变(42%)也明显减少。在类似条件下接种疫苗并受到攻击的金黄仓鼠,回收的虫体(83%)、肝脏虫卵(90%)、肠道虫卵(96%)、肝脏病变(56%)和虫体繁殖力(48 - 80%)均有所降低。这些数据表明,在ADAD疫苗接种系统中使用AA0029免疫调节剂配制rFh15可能是驱动针对血吸虫病产生有效免疫反应的一个良好选择。