Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, University of California Los Angeles (UCLA), UCLA AIDS Institute, Los Angeles, California, United States of America.
Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, United States of America.
PLoS Pathog. 2021 Jul 20;17(7):e1009738. doi: 10.1371/journal.ppat.1009738. eCollection 2021 Jul.
Broadly neutralizing antibodies (bNAbs) directed to HIV-1 have shown promise at suppressing viremia in animal models. However, the use of bNAbs for the central nervous system (CNS) infection is confounded by poor penetration of the blood brain barrier (BBB). Typically, antibody concentrations in the CNS are extremely low; with levels in cerebrospinal fluid (CSF) only 0.1% of blood concentrations. Using a novel nanotechnology platform, which we term nanocapsules, we show effective transportation of the human bNAb PGT121 across the BBB in infant rhesus macaques upon systemic administration up to 1.6% of plasma concentration. We demonstrate that a single dose of PGT121 encased in nanocapsules when delivered at 48h post-infection delays early acute infection with SHIVSF162P3 in infants, with one of four animals demonstrating viral clearance. Importantly, the nanocapsule delivery of PGT121 improves suppression of SHIV infection in the CNS relative to controls.
广谱中和抗体（bNAbs）针对 HIV-1 的研究在动物模型中显示出抑制病毒血症的潜力。然而，bNAbs 用于中枢神经系统（CNS）感染受到血脑屏障（BBB）通透性差的影响。通常，CNS 中的抗体浓度极低；脑脊液（CSF）中的水平仅为血液浓度的 0.1%。我们使用一种称为纳米胶囊的新型纳米技术平台，证明在婴儿恒河猴中，PGT121 这种人类 bNAb 可以通过全身给药有效地穿过 BBB，达到血浆浓度的 1.6%。我们证明，在感染后 48 小时给予纳米胶囊包裹的 PGT121 单剂量可延迟 SHIVSF162P3 对婴儿的早期急性感染，其中四只动物中有一只表现出病毒清除。重要的是，与对照组相比，PGT121 的纳米胶囊递送可改善对 CNS 中 SHIV 感染的抑制作用。
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