Centre for Strategic Planning and Management of Biomedical Health Risks, Federal Medical Biological Agency, 119992 Moscow, Russia.
Izmerov Research Institute of Occupational Health, 105275 Moscow, Russia.
Viruses. 2024 Aug 14;16(8):1296. doi: 10.3390/v16081296.
Anti-human immunodeficiency virus (HIV) broadly neutralizing antibodies (bNAbs) offer a promising approach for the treatment of HIV-1. The current paradigm for antibody therapy involves passive antibody transfer, requiring regular delivery of bNAbs in treating chronic diseases such as HIV-1. An alternative strategy is to use AAV-mediated gene transfer to enable in vivo production of desirable anti-HIV-1 antibodies. In this study, we investigated two sets of triple combinations of AAV9-vectors encoding different bNAbs: N6, 10E8, 10-1074 (CombiMab1), and VRC07-523, PGDM1400, 10-1074 (CombiMab2). We used CBAxC57Bl and C57BL/6 mouse models to characterize rAAV-induced antibody expression and to evaluate the neutralization capacity of mouse sera against a global panel of HIV-1 viral strains. rAAV9-mediated IgG expression varied between bNAb clones and mouse strains, with C57BL/6 mice exhibiting higher bNAb titers following rAAV delivery. Although CombiMab2 treatment elicited a higher IgG titer than CombiMab1, both combinations resulted in neutralization of all the viral strains from the global HIV-1 panel. Our data highlight the potential of AAV vectors as a long-term option for HIV-1 therapy.
抗人类免疫缺陷病毒 (HIV) 广谱中和抗体 (bNAbs) 为治疗 HIV-1 提供了一种很有前途的方法。目前的抗体治疗模式涉及被动抗体转移，需要定期输送 bNAbs 来治疗慢性疾病，如 HIV-1。另一种策略是使用 AAV 介导的基因转移，以实现体内产生理想的抗 HIV-1 抗体。在这项研究中，我们研究了两组编码不同 bNAbs 的 AAV9 载体的三联组合：N6、10E8、10-1074（CombiMab1）和 VRC07-523、PGDM1400、10-1074（CombiMab2）。我们使用 CBAxC57Bl 和 C57BL/6 小鼠模型来描述 rAAV 诱导的抗体表达，并评估小鼠血清对全球 HIV-1 病毒株的中和能力。rAAV9 介导的 IgG 表达在 bNAb 克隆和小鼠品系之间有所不同，C57BL/6 小鼠在 rAAV 递送后表现出更高的 bNAb 滴度。尽管 CombiMab2 治疗引起的 IgG 滴度高于 CombiMab1，但这两种组合都能中和来自全球 HIV-1 面板的所有病毒株。我们的数据强调了 AAV 载体作为 HIV-1 治疗的长期选择的潜力。
