Sánchez-Palencia Liz F, Trelis María, López-Abán Julio, Galiano Alicia, Vicente Belén, Del Olmo Esther, Muro Antonio, Bernal Dolores, Marcilla Antonio
Àrea de Parasitologia, Departament Farmàcia i Tecnologia Farmacèutica i Parasitologia, Universitat de València, 46100 Burjassot, Spain.
Unidad Mixta de Endocrinología, Nutrición y Dietética Clínica, Instituto de Investigación Sanitaria La Fe, 46026 Valencia, Spain.
Vaccines (Basel). 2022 Aug 10;10(8):1292. doi: 10.3390/vaccines10081292.
Strongyloidiasis, caused by is a neglected parasitic disease that represents a serious public health problem. In immunocompromised patients, this parasitosis can result in hyperinfection or disseminated disease with high levels of mortality. In previous studies, the mRNAs encoding for the 14-3-3 and major antigen proteins were found to be expressed at high levels in L3 larvae, suggesting potential key roles in parasite-host interactions. We have produced them as recombinant proteins (rSs14-3-3 and rSsMA) in a bacterial protein expression system. The serum levels of anti-rSs14-3-3 and anti-rSsMA IgGs are increased upon infection with validating the use of the mouse model since the native 14-3-3 and MA proteins induce an immune response. Each recombinant protein was formulated in the adjuvant adaptation (ADAD) vaccination system and injected twice, subcutaneously, in CD1 mice that were experimentally infected with 3000 L3 to evaluate their protective and immunomodulatory activity. Our results, including the number of parthenogenetic females, number of eggs in stool samples and the analysis of the splenic and intestinal indexes, show that the vaccines did not protect against infection. The immunization with rSs14-3-3 induced changes in the cytokine profile in mice, producing higher expression of IL-10, TGF-β, IL-13 and TNF-α in the spleen, suggesting a Th2/Treg-type response with an increase in TNF-α levels, confirming its role as an immunomodulator.
由粪类圆线虫引起的粪类圆线虫病是一种被忽视的寄生虫病，是一个严重的公共卫生问题。在免疫功能低下的患者中，这种寄生虫病可导致高度感染或播散性疾病，死亡率很高。在先前的研究中，发现编码14-3-3和主要抗原蛋白的mRNA在L3幼虫中高水平表达，表明在寄生虫与宿主的相互作用中可能起关键作用。我们已在细菌蛋白表达系统中将它们制备为重组蛋白（rSs14-3-3和rSsMA）。感染粪类圆线虫后，抗rSs14-3-3和抗rSsMA IgG的血清水平升高，这验证了小鼠模型的用途，因为天然的14-3-3和MA蛋白可诱导免疫反应。每种重组蛋白都在佐剂适应性（ADAD）疫苗接种系统中配制，并皮下注射两次到经3000条L3实验性感染的CD1小鼠中，以评估其保护和免疫调节活性。我们的结果，包括孤雌生殖雌性的数量、粪便样本中的卵数以及脾脏和肠道指数的分析，表明这些疫苗不能预防感染。用rSs14-3-3免疫诱导了小鼠细胞因子谱的变化，使脾脏中IL-10、TGF-β、IL-13和TNF-α的表达更高，表明是一种Th2/Treg型反应，TNF-α水平升高，证实了其作为免疫调节剂的作用。
