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用于评估HIV-1预防性疫苗策略的非人灵长类动物模型:模型参数考量及影响

Nonhuman primate models for the evaluation of HIV-1 preventive vaccine strategies: model parameter considerations and consequences.

作者信息

Del Prete Gregory Q, Lifson Jeffrey D, Keele Brandon F

机构信息

AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.

出版信息

Curr Opin HIV AIDS. 2016 Nov;11(6):546-554. doi: 10.1097/COH.0000000000000311.

Abstract

PURPOSE OF REVIEW

Nonhuman primate (NHP) models of AIDS are powerful systems for evaluating HIV vaccine approaches in vivo. Authentic features of HIV-1 transmission, dissemination, target cell tropism, and pathogenesis, and aspects of anti-HIV-1 immune responses, can be recapitulated in NHPs provided the appropriate, specific model parameters are considered. Here, we discuss key model parameter options and their implications for HIV-1 vaccine evaluation.

RECENT FINDINGS

With the availability of several different NHP host species/subspecies, different challenge viruses and challenge stock production methods, and various challenge routes and schemata, multiple NHP models of AIDS exist for HIV vaccine evaluation. The recent development of multiple new challenge viruses, including chimeric simian-human immunodeficiency viruses and simian immunodeficiency virus clones, improved characterization of challenge stocks and production methods, and increased insight into specific challenge parameters have resulted in an increase in the number of available models and a better understanding of the implications of specific study design choices.

SUMMARY

Recent progress and technical developments promise new insights into basic disease mechanisms and improved models for better preclinical evaluation of interventions to prevent HIV transmission.

摘要

综述目的

艾滋病非人灵长类动物(NHP)模型是在体内评估HIV疫苗方法的强大系统。只要考虑适当的特定模型参数,HIV-1传播、扩散、靶细胞嗜性和发病机制的真实特征以及抗HIV-1免疫反应的各个方面都可以在非人灵长类动物中重现。在此,我们讨论关键模型参数选项及其对HIV-1疫苗评估的影响。

最新发现

由于有几种不同的非人灵长类动物宿主物种/亚种、不同的攻击病毒和攻击毒株生产方法以及各种攻击途径和方案,存在多种用于HIV疫苗评估的艾滋病非人灵长类动物模型。多种新攻击病毒的近期开发,包括嵌合猿猴-人类免疫缺陷病毒和猿猴免疫缺陷病毒克隆,改进了对攻击毒株和生产方法的表征,以及对特定攻击参数的深入了解,导致可用模型数量增加,并更好地理解了特定研究设计选择的影响。

总结

近期的进展和技术发展有望为基本疾病机制带来新的见解,并改进模型,以便更好地对预防HIV传播的干预措施进行临床前评估。

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