PDF(Pubmed)
Abstract：
Understanding infectious disease pathogenesis and evaluating novel candidate treatment interventions for human use frequently requires prior or parallel analysis in animal model systems. While rodent species are frequently applied in such studies, there are situations where non-human primate (NHP) species are advantageous or required. These include studies of animals that are anatomically more akin to humans, where there is a need to interrogate the complexity of more advanced biological systems or simply reflect susceptibility to a specific infectious agent. The contribution of different arms of the immune response may be addressed in a variety of NHP species or subspecies in specific physiological compartments. Such studies provide insights into immune repertoires not always possible from human studies. However, genetic variation in outbred NHP models may confound, or significantly impact the outcome of a particular study. Thus, host factors need to be considered when undertaking such studies. Considerable knowledge of the impact of host immunogenetics on infection dynamics was elucidated from HIV/SIV research. NHP models are now important for studies of emerging infections. They have contributed to delineating the pathogenesis of SARS-CoV-2/COVID-19, which identified differences in outcomes attributable to the selected NHP host. Moreover, their use was crucial in evaluating the immunogenicity and efficacy of vaccines against COVID-19 and establishing putative correlates of vaccine protection. More broadly, neglected or highly pathogenic emerging or re-emergent viruses may be studied in selected NHPs. These studies characterise protective immune responses following infection or the administration of candidate immunogens which may be central to the accelerated licensing of new vaccines. Here, we review selected aspects of host immunogenetics, specifically MHC background and TRIM5 polymorphism as exemplars of adaptive and innate immunity, in commonly used Old and New World host species. Understanding this variation within and between NHP species will ensure that this valuable laboratory source is used most effectively to combat established and emerging virus infections and improve human health worldwide.
摘要：
了解传染病发病机理和评估人类使用的新型候选治疗干预措施通常需要在动物模型系统中进行事先或并行分析。虽然啮齿动物物种经常被应用在这样的研究中，存在非人灵长类动物(NHP)物种是有利的或需要的情况。这些包括对解剖学上更类似于人类的动物的研究，需要询问更先进的生物系统的复杂性或简单地反映对特定传染因子的易感性。免疫应答的不同臂的贡献可以在特定生理区室中的多种NHP物种或亚种中解决。这样的研究提供了对人类研究中不总是可能的免疫库的见解。然而,近交NHP模型中的遗传变异可能会混淆，或显著影响特定研究的结果。因此，进行此类研究时需要考虑宿主因素。从HIV/SIV研究中阐明了宿主免疫遗传学对感染动力学的影响的大量知识。NHP模型现在对于新出现的感染的研究很重要。他们有助于描述SARS-CoV-2/COVID-19的发病机理，从而确定了归因于选定NHP宿主的结果差异。此外，它们的使用对于评估抗COVID-19疫苗的免疫原性和功效以及建立疫苗保护的假定相关性至关重要.更广泛地说,可以在选定的NHP中研究被忽视或高致病性的新出现或重新出现的病毒。这些研究描述了感染或施用候选免疫原后的保护性免疫应答，这可能是加速新疫苗许可的核心。这里,我们回顾了宿主免疫遗传学的选定方面，特别是MHC背景和TRIM5多态性作为适应性和先天免疫的范例，在常用的旧世界和新世界寄主物种中。了解NHP物种内部和之间的这种差异将确保最有效地使用这一宝贵的实验室来源来对抗已建立和新出现的病毒感染并改善全球人类健康。
