Stijlemans Benoit, De Baetselier Patrick, Caljon Guy, Van Den Abbeele Jan, Van Ginderachter Jo A, Magez Stefan
Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel (VUB), Brussels, Belgium.
Myeloid Cell Immunology Lab, VIB-UGent Center for Inflammation Research, Ghent, Belgium.
Front Immunol. 2017 Jun 30;8:724. doi: 10.3389/fimmu.2017.00724. eCollection 2017.
African trypanosomes are strictly extracellular protozoan parasites that cause diseases in humans and livestock and significantly affect the economic development of sub-Saharan Africa. Due to an elaborate and efficient (vector)-parasite-host interplay, required to complete their life cycle/transmission, trypanosomes have evolved efficient immune escape mechanisms that manipulate the entire host immune response. So far, not a single field applicable vaccine exists, and chemotherapy is the only strategy available to treat the disease. Current therapies, however, exhibit high drug toxicity and an increased drug resistance is being reported. In addition, diagnosis is often hampered due to the inadequacy of current diagnostic procedures. In the context of tackling the shortcomings of current treatment and diagnostic approaches, nanobodies (Nbs, derived from the heavy chain-only antibodies of camels and llamas) might represent unmet advantages compared to conventional tools. Indeed, the combination of their small size, high stability, high affinity, and specificity for their target and tailorability represents a unique advantage, which is reflected by their broad use in basic and clinical research to date. In this article, we will review and discuss (i) diagnostic and therapeutic applications of Nbs that are being evaluated in the context of African trypanosomiasis, (ii) summarize new strategies that are being developed to optimize their potency for advancing their use, and (iii) document on unexpected properties of Nbs, such as inherent trypanolytic activities, that besides opening new therapeutic avenues, might offer new insight in hidden biological activities of conventional antibodies.
非洲锥虫是严格的细胞外原生动物寄生虫，可导致人类和牲畜患病，并严重影响撒哈拉以南非洲的经济发展。由于完成其生命周期/传播需要精心且高效的（媒介）-寄生虫-宿主相互作用，锥虫进化出了有效的免疫逃逸机制，可操纵整个宿主免疫反应。到目前为止，尚无一种适用于现场的疫苗，化疗是治疗该疾病的唯一可用策略。然而，目前的疗法显示出高药物毒性，且耐药性不断增加。此外，由于当前诊断程序的不足，诊断常常受到阻碍。在解决当前治疗和诊断方法的缺点的背景下，纳米抗体（源自骆驼和羊驼仅重链抗体的Nbs）与传统工具相比可能具有尚未被发掘的优势。事实上，它们体积小、稳定性高、亲和力高、对靶点具有特异性以及可定制性的结合代表了独特的优势，这一点从它们迄今为止在基础和临床研究中的广泛应用中得到了体现。在本文中，我们将回顾和讨论（i）在非洲锥虫病背景下正在评估的纳米抗体的诊断和治疗应用，（ii）总结正在开发的优化其效力以促进其应用的新策略，以及（iii）记录纳米抗体的意外特性，如固有的溶锥虫活性，这除了开辟新的治疗途径外，可能还会为传统抗体隐藏的生物学活性提供新的见解。
