Virus-like particles: designing an effective AIDS vaccine.
Virus-like particles: designing an effective AIDS vaccine.
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DOI：
10.1016/j.ymeth.2006.05.024
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发表时间：
2006-09
期刊：
影响因子：
4.8
通讯作者：
K. Young;Sean P Mcburney;L. Karkhanis;T. Ross
中科院分区：
文献类型：
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作者：
K. Young;Sean P Mcburney;L. Karkhanis;T. Ross
感染真核生物的病毒具有自组装成颗粒的独特特征。哺乳动物的免疫系统高度适应于在感染后识别和攻击这些病毒颗粒。使用基于颗粒的免疫原，通常作为减毒活病毒递送，已成为多种病毒的有效疫苗接种策略。针对人类免疫缺陷病毒（HIV）的有效疫苗的开发已被证明是一个挑战，因为HIV感染免疫系统的细胞，引起严重的免疫缺陷，导致称为AIDS的综合征。此外，病毒适应免疫压力并以整合形式存在于宿主细胞中的能力也是疫苗学家需要克服的障碍。基于颗粒的疫苗策略有希望引发针对不同HIV抗原的多种病毒表位的高滴度、长寿命的免疫应答。减毒活病毒可有效产生细胞和体液免疫应答。然而，虽然这些疫苗刺激免疫力，但受攻击的动物很少清除病毒感染，并且减毒程度与疾病保护直接相关。此外，减毒活疫苗具有回复到致病形式的潜力。或者，病毒样颗粒（VLP）模拟病毒颗粒而不引起免疫缺陷疾病。VLP是自组装的、非复制的、非致病性的颗粒，其在大小和构象上与完整病毒体相似。用于慢病毒的多种VLP目前处于临床前和临床试验中。本文综述了基于VLP的艾滋病疫苗的研究现状，包括动物实验和临床试验的纯化和免疫设计。
Viruses that infect eukaryotic organisms have the unique characteristic of self-assembling into particles. The mammalian immune system is highly attuned to recognizing and attacking these viral particles following infection. The use of particle-based immunogens, often delivered as live-attenuated viruses, has been an effective vaccination strategy for a variety of viruses. The development of an effective vaccine against the human immunodeficiency virus (HIV) has proven to be a challenge, since HIV infects cells of the immune system causing severe immunodeficiency resulting in the syndrome known as AIDS. In addition, the ability of the virus to adapt to immune pressure and reside in an integrated form in host cells presents hurdles for vaccinologists to overcome. A particle-based vaccine strategy has promise for eliciting high titer, long-lived, immune responses to a diverse number of viral epitopes against different HIV antigens. Live-attenuated viruses are effective at generating both cellular and humoral immune responses. However, while these vaccines stimulate immunity, challenged animals rarely clear the viral infection and the degree of attenuation directly correlates with protection from disease. Further, a live-attenuated vaccine has the potential to revert to a pathogenic form. Alternatively, virus-like particles (VLPs) mimic the viral particle without causing an immunodeficiency disease. VLPs are self-assembling, non-replicating, non-pathogenic particles that are similar in size and conformation to intact virions. A variety of VLPs for lentiviruses are currently in preclinical and clinical trials. This review focuses on our current status of VLP-based AIDS vaccines, regarding issues of purification and immune design for animal and clinical trials.