Young Kelly R, Ross Ted M
Department of Microbiology and Immunology, East Carolina University School of Medicine, Greenville, North Carolina 27858, USA.
Curr Drug Targets Infect Disord. 2003 Jun;3(2):151-69. doi: 10.2174/1568005033481213.
The use of live-attenuated viruses as vaccines has been successful for the control of viral infections. However, the development of an effective vaccine against the human immunodeficiency virus (HIV) has proven to be a challenge. HIV infects cells of the immune system and results in a severe immunodeficiency. In addition, the ability of the virus to adapt to immune pressure and the ability to reside in an integrated form in host cells present 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 from different HIV antigens. Live-attenuated viruses are effective at generating both cellular and humoral immunity, however, a live-attenuated vaccine for HIV is problematic. The possibility of a live-attenuated vaccine to revert to a pathogenic form or recombine with a wild-type or defective virus in an infected individual is a drawback to this approach. Therefore, these vaccines are currently only being tested in non-human primate models. Live-attenuated vaccines are effective in stimulating immunity, however challenged animals rarely clear viral infection and the degree of attenuation directly correlates with the protection of animals from disease. Another particle-based vaccine approach for HIV involves the use of virus-like particles (VLPs). VLPs mimic the viral particle without causing an immunodeficiency disease. HIV-like particles (HIV-LP) are defined as self-assembling, non-replicating, nonpathogenic, genomeless particles that are similar in size and conformation to intact virions. A variety of VLPs for both HIV and SIV are currently in pre-clinical and clinical trials. This review focuses on the current knowledge regarding the immunogenicity and safety of particle-based vaccine strategies for HIV-1.
使用减毒活病毒作为疫苗已成功用于控制病毒感染。然而，事实证明，开发一种有效的抗人类免疫缺陷病毒（HIV）疫苗是一项挑战。HIV感染免疫系统细胞并导致严重的免疫缺陷。此外，该病毒适应免疫压力的能力以及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来自不同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方面都很有效，然而，用于HIV的减毒活疫苗存在问题。减毒活疫苗在受感染个体中恢复为致病形式或与野生型或缺陷病毒重组的可能性是这种方法的一个缺点。因此，目前这些疫苗仅在非人类灵长类动物模型中进行测试。减毒活疫苗在刺激免疫方面有效，然而，受挑战的动物很少能清除病毒感染，并且减毒程度与动物免受疾病的保护直接相关。另一种用于HIV的基于颗粒的疫苗方法涉及使用病毒样颗粒（VLP）。VLP模仿病毒颗粒而不引起免疫缺陷疾病。HIV样颗粒（HIV-LP）被定义为自组装、非复制、无致病性、无基因组的颗粒，其大小和构象与完整病毒粒子相似。目前，多种针对HIV和SIV的VLP正处于临床前和临床试验阶段。本综述重点关注目前关于HIV-1基于颗粒的疫苗策略的免疫原性和安全性的知识。
