Conteh Solomon, Anderson Charles, Lambert Lynn, Orr-Gonzalez Sachy, Herrod Jessica, Robbins Yvette L, Carter Dariyen, Karhemere Stomy Bin Shamamba, Pyana Pati, Büscher Philippe, Duffy Patrick E
Laboratory of Malaria Immunology and Vaccinology (LMIV), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Rockville, Maryland.
Department of Parasitology, Institut National de Recherche Biomédicale (INRB), Kinshasa, Democratic Republic of Congo.
Am J Trop Med Hyg. 2017 Apr;96(4):835-841. doi: 10.4269/ajtmh.16-0745. Epub 2017 Jan 23.
AbstractInbred mice are commonly used to test candidate malaria vaccines, but have been unreliable for predicting efficacy in humans. To establish a more rigorous animal model, we acquired African woodland thicket rats of the genus , the natural hosts for . Thicket rats were acquired and identified as by skull and teeth measurements and mitochondrial DNA genotyping. Herein, we demonstrate that thicket rats are highly susceptible to infection by , and moderately susceptible to and : 1-2 infected mosquito bites or 25-100 sporozoites administered by intravenous injection consistently resulted in patent parasitemia with , and resulted in patent parasitemia with and strains for at least 50% of animals. We then assessed efficacy of whole-organism vaccines to induce sterile immunity, and compared the thicket rat model to conventional mouse models. Using ANKA radiation-attenuated sporozoites, and ANKA and chemoprophylaxis vaccination approaches, we found that standard doses of vaccine sufficient to protect laboratory mice for a long duration against malaria challenge, are insufficient to protect thicket rats, which require higher doses of vaccine to achieve even short-term sterile immunity. Thicket rats may offer a more stringent and pertinent model for evaluating whole-organism vaccines.
摘要
近交系小鼠常用于测试候选疟疾疫苗，但在预测人体疗效方面并不可靠。为建立一个更严格的动物模型，我们获取了 属的非洲林地灌丛大鼠，它们是 的天然宿主。通过头骨和牙齿测量以及线粒体DNA基因分型获取并鉴定灌丛大鼠为 。在此，我们证明灌丛大鼠对 感染高度易感，对 和 中度易感：1 - 2次感染性蚊虫叮咬或静脉注射25 - 100个子孢子始终会导致 出现明显的寄生虫血症，并且至少50%的动物感染 和 毒株后会出现明显的寄生虫血症。然后，我们评估了全生物体疫苗诱导无菌免疫的效果，并将灌丛大鼠模型与传统小鼠模型进行了比较。使用 减毒辐射子孢子以及 、 化学预防疫苗接种方法，我们发现足以长期保护实验小鼠免受疟疾攻击的标准剂量疫苗，不足以保护灌丛大鼠，灌丛大鼠需要更高剂量的疫苗才能实现哪怕是短期的无菌免疫。灌丛大鼠可能为评估全生物体疫苗提供一个更严格且相关的模型。
