Improved delivery of broadly neutralizing antibodies by nanocapsules suppresses SHIV infection in the CNS of infant rhesus macaques

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...

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Bibliographic Details
Published in:PLoS pathogens 2021-07, Vol.17 (7), p.e1009738-e1009738
Main Authors: Wen, Jing, Cheever, Tracy, Wang, Lan, Wu, Di, Reed, Jason, Mascola, John, Chen, Xuejun, Liu, Cuiping, Pegu, Amarendra, Sacha, Jonah B, Lu, Yunfeng, Haigwood, Nancy L, Chen, Irvin S. Y
Format: Article
Language:English
Subjects:
Acquired immune deficiency syndrome
AIDS
Animal models
Animals
Antibodies
Babies
Biology and Life Sciences
Blood
Blood-brain barrier
Brain
Care and treatment
Central nervous system
Central nervous system diseases
Cerebrospinal fluid
Clinical trials
Design and construction
Drug delivery devices
Health aspects
HIV
HIV infection
Human immunodeficiency virus
Immunotherapy
Infants
Infections
Medical research
Medicine and Health Sciences
Medicine, Experimental
Metastasis
Nanomedicine
Nanoparticles
Nanotechnology
Neurological disorders
Neutralizing
Plasma
Research and Analysis Methods
Testing
Viral antibodies
Viral infections
Viremia
Viruses
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Summary: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 SHIV SF162P3 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.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1009738