# Improved delivery of bNAbs for targeting CNS infection in infants

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $843,177

## Abstract

PROJECT SUMMARY
 Despite the tremendous success of the combination antiretroviral therapy (cART), the persistence of HIV
reservoirs remains as the major obstacle to achieve HIV cure in infants. Current strategies mainly focus on the
peripheral reservoirs; however, their efficacy is limited in the central nerve system (CNS) due to its unique
anatomy. Extensive studies indicate that replication-competent reservoirs persist in the CNS under cART,
causing neurological disorders in 15-55% of HIV+ individuals on cART. This issue is particularly concerning for
infants, whose brains still grow and develop, leading to numerous neurodevelopment consequences and
neurologic diseases. Therefore, there is an urgent need for effective treatment to suppress CNS infection in
infants. One promising strategy is the use of broadly neutralizing antibodies (bNAb) directed to HIV-1, which
have demonstrated potential in both viral suppression and reservoir clearance in animal models and clinical trials.
However, the use of bNAbs for the CNS reservoirs is confounded by poor penetration of the blood brain barrier
(BBB). Typically, antibody concentrations in the CNS are extremely low, with cerebrospinal fluid (CSF) levels at
~0.1% of those in blood. Our team has developed a novel nanotechnology, which we term nanocapsules, to
encapsulate bNAb molecules within polymer shells, of which the surface contains abundant choline analogues.
Such nanocapsules can effectively deliver bNAbs into the CNS by binding to the choline transporter on the BBB
upon systemic administration, showing promising results in suppressing the virus in the CNS of non-human
primate (NHP) infants.
 Our understanding of CNS infections and associated neuroinflammation during early infection and early
treatment is still limited. Recent advances in molecular biology, nucleotide sequencing, and bioinformatics have
enabled our team to develop methods to track infected cell clones with viral integration sites, revealing the impact
of therapy on clonally expanded virus-infected cells. We are also exploring the use of a library of barcoded
viruses for population-level analysis of infection in latent reservoirs and following HIV rebound.
 In this proposed study, we aim to evaluate the efficacy of bNAbs in nanocapsules against CNS infections
and reservoirs, both with and without cART. The success of this study will shed light on the mechanisms
underlying CNS infections in infants and demonstrate the effectiveness of bNAbs with improved CNS delivery in
suppressing CNS and deep tissue infections and reservoirs. The findings could lead to interventions that can be
initiated within the first few weeks of infection, a critical period associated with reduced mortality and slower HIV
progression in infants.

## Key facts

- **NIH application ID:** 11085596
- **Project number:** 1R01NS137919-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Ann Jones Hessell
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $843,177
- **Award type:** 1
- **Project period:** 2024-09-18 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11085596

## Citation

> US National Institutes of Health, RePORTER application 11085596, Improved delivery of bNAbs for targeting CNS infection in infants (1R01NS137919-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/11085596. Licensed CC0.

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