Wolf Roman F, Papin James F, Hines-Boykin Rebecca, Chavez-Suarez Maria, White Gary L, Sakalian Michael, Dittmer Dirk P
Department of Comparative Medicine Science, University of Oklahoma Health Sciences Center, USA.
Virology. 2006 Nov 10;355(1):44-51. doi: 10.1016/j.virol.2006.06.033. Epub 2006 Aug 10.
Animal models that closely mimic the human condition are of paramount significance to study pathogenic mechanisms, vaccine and therapy scenarios. This is particularly true for investigations that involve emerging infectious diseases. Nonhuman primate species represent an alternative to the more intensively investigated rodent animal models and in a number of instances have been shown to represent a more reliable predictor of the human response to infection. West Nile virus (WNV) has emerged as a new pathogen in the Americas. It has a 5% fatality rate, predominantly in the elderly and immune compromised. Typically, infections are cleared by neutralizing antibodies, which suggests that a vaccine would be efficacious. Previously, only macaques had been evaluated as a primate model for WNV vaccine design. The macaques did not develop WNV disease nor express the full complement of IgG subclasses that is found in humans. We therefore explored baboons, which exhibit the similar four IgG subclasses observed in humans as a new model for WNV infection and vaccine evaluation. In this present report, we describe the experimental infection of baboons with WNV and test the efficacy of an inactivated WNV vaccination strategy. All experimentally infected animals developed transient viremia and subsequent neutralizing antibodies. Anti-WNV IgM antibodies peaked at 20 days post-infection. Anti-WNV IgG antibodies appeared later and persisted past 60 days. Prior vaccination with chemically inactivated virus induced neutralizing titers and a fast, high titer IgG recall response, which resulted in lower viremia upon challenge. This report is the first to describe the development of the baboon model for WNV experimental infection and the utility of this model to characterize the immunologic response against WNV and a candidate WNV vaccine.
紧密模拟人类疾病状况的动物模型对于研究致病机制、疫苗和治疗方案至关重要。对于涉及新发传染病的研究而言尤其如此。非人灵长类动物是比研究更为深入的啮齿动物模型更好的选择，并且在许多情况下已被证明能更可靠地预测人类对感染的反应。西尼罗河病毒（WNV）已在美洲成为一种新的病原体。它的致死率为5%，主要发生在老年人和免疫功能低下者中。通常，感染通过中和抗体清除，这表明疫苗可能有效。此前，只有猕猴被评估为WNV疫苗设计的灵长类动物模型。猕猴并未患上WNV疾病，也未表达出人类中发现的完整IgG亚类。因此，我们探索了狒狒，其表现出与人类相似的四种IgG亚类，作为WNV感染和疫苗评估的新模型。在本报告中，我们描述了用WNV对狒狒进行实验性感染，并测试了灭活WNV疫苗接种策略的效果。所有实验感染的动物都出现了短暂的病毒血症和随后的中和抗体。抗WNV IgM抗体在感染后20天达到峰值。抗WNV IgG抗体出现较晚，并且在60天后仍持续存在。预先用化学灭活病毒进行疫苗接种诱导了中和抗体滴度以及快速、高滴度的IgG回忆反应，这导致在再次感染时病毒血症较低。本报告首次描述了用于WNV实验性感染的狒狒模型的建立，以及该模型在表征针对WNV的免疫反应和候选WNV疫苗方面的实用性。
