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抗艾滋病毒/艾滋病的抗体介导疗法:我们目前的进展如何?

Antibody-Mediated Therapy against HIV/AIDS: Where Are We Standing Now?

作者信息

Awi Noel Jacques, Teow Sin-Yeang

机构信息

Department of Medical Sciences (DMS), School of Healthcare and Medical Sciences (SHMS), Sunway University, Jalan Universiti, Bandar Sunway, 47500 Subang Jaya, Selangor Darul Ehsan, Malaysia.

出版信息

J Pathog. 2018 Jun 3;2018:8724549. doi: 10.1155/2018/8724549. eCollection 2018.

Abstract

Acquired immunodeficiency syndrome (AIDS) cases are on the rise globally. To date, there is still no effective measure to eradicate the causative agent, human immunodeficiency virus (HIV). Highly active antiretroviral therapy (HAART) is being used in HIV/AIDS management, but it results in long-term medication and has major drawbacks such as multiple side effects, high cost, and increasing the generation rate of escape mutants. In addition, HAART does not control HIV-related complications, and hence more medications and further management are required. With this, other alternatives are urgently needed. In the past, small-molecule inhibitors have shown potent antiviral effects, and some of them are now being evaluated in clinical trials. The challenges in developing these small molecules for clinical use include the off-target effect, poor stability, and low bioavailability. On the other hand, antibody-mediated therapy has emerged as an important therapeutic modality for anti-HIV therapeutics development. Many antiviral antibodies, namely, broad neutralizing antibodies (bnAbs) against multiple strains of HIV, have shown promising effects and in animal studies; further studies are ongoing in clinical trials to evaluate their uses in clinical applications. This short review aims to discuss the current development of therapeutic antibodies against HIV and the challenges in adopting them for clinical use.

摘要

获得性免疫缺陷综合征(艾滋病)病例在全球范围内呈上升趋势。迄今为止,仍没有根除病原体人类免疫缺陷病毒(HIV)的有效措施。高效抗逆转录病毒疗法(HAART)被用于HIV/AIDS的治疗,但它需要长期用药,且存在诸多主要缺点,如多种副作用、成本高昂以及增加逃逸突变体的产生率。此外,HAART无法控制与HIV相关的并发症;因此,需要更多药物和进一步的治疗。据此,迫切需要其他替代方案。过去,小分子抑制剂已显示出强大的抗病毒作用,其中一些目前正在临床试验中进行评估。将这些小分子开发用于临床的挑战包括脱靶效应、稳定性差和生物利用度低。另一方面,抗体介导的疗法已成为抗HIV治疗药物开发的一种重要治疗方式。许多抗病毒抗体,即针对多种HIV毒株的广泛中和抗体(bnAbs),在动物研究中已显示出有前景的效果;目前正在进行进一步的临床试验,以评估它们在临床应用中的用途。这篇简短的综述旨在讨论抗HIV治疗性抗体的当前进展以及将它们用于临床所面临的挑战。

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