Young Kelly R, McBurney Sean P, Karkhanis Lukena U, Ross Ted M
Department of Medicine, Division of Infectious Diseases, University of Pittsburgh School of Medicine, PA 15261, USA.
Methods. 2006 Sep;40(1):98-117. doi: 10.1016/j.ymeth.2006.05.024.
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.
感染真核生物的病毒具有自我组装成颗粒的独特特性。哺乳动物免疫系统对感染后识别并攻击这些病毒颗粒高度敏感。使用通常以减毒活病毒形式递送的基于颗粒的免疫原，一直是针对多种病毒的有效疫苗接种策略。事实证明，开发一种有效的抗人类免疫缺陷病毒（HIV）疫苗具有挑战性，因为HIV感染免疫系统细胞，导致严重免疫缺陷，进而引发被称为艾滋病的综合征。此外，该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，给疫苗学家带来了需要克服的障碍。基于颗粒的疫苗策略有望引发针对不同HIV抗原的多种病毒表位的高滴度、长效免疫反应。减毒活病毒在产生细胞免疫和体液免疫反应方面都很有效。然而，虽然这些疫苗能刺激免疫，但受攻击的动物很少能清除病毒感染，而且减毒程度与对疾病的保护直接相关。此外，减毒活疫苗有可能恢复为致病形式。相比之下，病毒样颗粒（VLP）模仿病毒颗粒但不会引发免疫缺陷疾病。VLP是自我组装、非复制、无致病性的颗粒，其大小和构象与完整病毒粒子相似。目前，多种针对慢病毒的VLP正处于临床前和临床试验阶段。本综述重点关注基于VLP的艾滋病疫苗的当前状况，涉及动物和临床试验的纯化及免疫设计问题。
