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

Jing Wen, Tracy Cheever, Lan Wang, Di Wu, Jason Reed, John Mascola, Xuejun Chen, Cuiping Liu, Amarendra Pegu, Jonah B. Sacha, Yunfeng Lu, Nancy L. Haigwood, Irvin S.Y. Chen

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article numbere1009738
JournalPLoS pathogens
Volume17
Issue numberJuly
DOIs
StatePublished - Jul 2021

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

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