# Pediatric Adolescent Virus Elimination (PAVE) Martin Delaney Collaboratory

> **NIH NIH UM1** · JOHNS HOPKINS UNIVERSITY · 2024 · $432,188

## Abstract

ABSTRACT
SIGNIFICANCE:
HIV has been shown to seed in the central nervous system (CNS) during primary viremia and serve as a
reservoir of HIV (PMCID: PMC10266791, PMC32332225). In addition to latent reservoirs, replication-
competent reservoirs are believed to persist in the CNS during cART (PMID: PMC31790378, PMC5831193,
PMC5044815, PMC5559639, PMC7896558). This is particularly concerning for infants as their brains grow
and develop, leading to numerous neurodevelopment consequences (PMID: 24125015) and neurologic
diseases (PMID: 24806816). Compared to peripheral infection and reservoirs, current understandings of CNS
infection and associated neuroinflammation during early infection and under early treatment are limited.
Advances in molecular biology, nucleotide sequencing, and bioinformatic approaches have allowed our team
to develop a strategy to track infected cell clones with viral integration sites to show the impact of therapy on
virus infected clonally expanded cells (PMID: 32766447, PMID: 25289675, PMID: 24702996, PMID: 20844053,
PMID: 28654067). Moreover, we explore the utility of a library of barcoded viruses to achieve a population level
analysis of infection in latent reservoirs and after HIV rebound (PMID: 33377133, PMID: 35013215). Here,
these technologies will be adapted to assess the impact of bNAbs on SHIV CNS infection.
AIMS:
In this project, we propose to examine in detail the early dynamics and neuroinflammation of CNS infection in
the SHIV infant macaque model established at the ONPRC. We have established unique molecular
approaches to delineate CNS infection and reservoirs and their changes responding to treatment. Our team
uses a library of barcoded viruses to quantify the frequency of tagged viruses which are integrated, and the
relative level of each tagged virus produced in the periphery and the CNS. We have also developed high
throughput sequence analysis of viral integration sites, which enables quantitation of clonal expansion of
infected cells. Both assays together provide sensitive and quantitative means to assess the impact of therapy
upon the contribution of infected cells to the SHIV reservoir in the CNS. In Aim 2, we will further test a novel
therapeutic strategy aimed towards CNS infection suppression and clearance through effective delivery of
nanocapsuled bNAb in the CNS. Importantly, our CNS-delivered nanocapsules can be extended to various
bNAbs and other therapeutics (e.g., other immunotherapeutics, gene-editing agents, anti-viral drugs), opening
a new avenue for the development of novel HIV therapeutics.
IMPACT:
The success of this study will begin to dissect the mechanisms underlying CNS infection in infants and
demonstrate the effectiveness of bNAbs with improved CNS delivery to suppress CNS and deep tissue
infection and reservoirs. The successful completion of this project and acquired knowledge may lead to
interventions that could be initiated within the first few weeks of infection, the window of opp...

## Key facts

- **NIH application ID:** 11093637
- **Project number:** 3UM1AI164566-04S2
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Ann M Chahroudi
- **Activity code:** UM1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $432,188
- **Award type:** 3
- **Project period:** 2021-08-16 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11093637

## Citation

> US National Institutes of Health, RePORTER application 11093637, Pediatric Adolescent Virus Elimination (PAVE) Martin Delaney Collaboratory (3UM1AI164566-04S2). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11093637. Licensed CC0.

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