Sariol Carlos A, White Laura J
Department of Microbiology and Medical Zoology, Caribbean Primate Research Center, University of Puerto Rico-Medical Sciences Campus , San Juan, PR , USA ; Department of Internal Medicine, Caribbean Primate Research Center, University of Puerto Rico-Medical Sciences Campus , San Juan, PR , USA.
Global Vaccine Incorporation , Research Triangle Park, NC , USA.
Front Immunol. 2014 Sep 24;5:452. doi: 10.3389/fimmu.2014.00452. eCollection 2014.
Dengue is considered the most important emerging, human arboviruses, with worldwide distribution in the tropics. Unfortunately, there are no licensed dengue vaccines available or specific anti-viral drugs. The development of a dengue vaccine faces unique challenges. The four serotypes co-circulate in endemic areas, and pre-existing immunity to one serotype does not protect against infection with other serotypes, and actually may enhance severity of disease. One foremost constraint to test the efficacy of a dengue vaccine is the lack of an animal model that adequately recapitulates the clinical manifestations of a dengue infection in humans. In spite of this limitation, non-human primates (NHP) are considered the best available animal model to evaluate dengue vaccine candidates due to their genetic relatedness to humans and their ability to develop a viremia upon infection and a robust immune response similar to that in humans. Therefore, most dengue vaccines candidates are tested in primates before going into clinical trials. In this article, we present a comprehensive review of published studies on dengue vaccine evaluations using the NHP model, and discuss critical parameters affecting the usefulness of the model. In the light of recent clinical data, we assess the ability of the NHP model to predict immunological parameters of vaccine performances in humans and discuss parameters that should be further examined as potential correlates of protection. Finally, we propose some guidelines toward a more standardized use of the model to maximize its usefulness and to better compare the performance of vaccine candidates from different research groups.
登革热被认为是最重要的新发人类虫媒病毒，在热带地区呈全球分布。不幸的是，目前尚无获批的登革热疫苗或特异性抗病毒药物。登革热疫苗的研发面临着独特的挑战。四种血清型在流行地区共同传播，对一种血清型的既往免疫不能预防其他血清型的感染，实际上还可能加重疾病的严重程度。测试登革热疫苗疗效的一个首要限制是缺乏能够充分重现人类登革热感染临床表现的动物模型。尽管存在这一局限性，但由于非人灵长类动物（NHP）与人类具有遗传相关性，且感染后能够产生病毒血症并引发与人类相似的强烈免疫反应，因此被认为是评估登革热候选疫苗的最佳可用动物模型。因此，大多数登革热候选疫苗在进入临床试验之前都要在灵长类动物身上进行测试。在本文中，我们对使用NHP模型进行登革热疫苗评估的已发表研究进行了全面综述，并讨论了影响该模型实用性的关键参数。根据最近的临床数据，我们评估了NHP模型预测人类疫苗性能免疫参数的能力，并讨论了应作为潜在保护相关性进一步研究的参数。最后，我们提出了一些指导方针，以更规范地使用该模型，最大限度地发挥其作用，并更好地比较不同研究组候选疫苗的性能。
