# Targeting the HIV-1 reservoir with a combination of an IDLV-SIVGag therapeutic vaccine and Fc-engineered bnAbs

> **NIH NIH R56** · DUKE UNIVERSITY · 2020 · $760,086

## Abstract

ABSTRACT
The development of therapeutic interventions that can target viral reservoirs in HIV-1 infected individuals
is a major goal of HIV-1 research. Recent evidence that infusion of HIV-1 specific broadly neutralizing
antibodies (bnAbs) in chronically SHIV-infected macaques resulted in transient suppression of viremia
and reduction of proviral DNA in both peripheral blood and tissues, have led to renewed interest in the
development of therapeutic strategies that can improve the control of virus rebound after anti-retroviral
treatment (ART) interruption and diminish the viral reservoir size. Extending the bnAbs circulation half-
lives and improving their ability to mediate killing of infected cells though engineering of the Fc region is
a viable strategy to enhance bnAbs impact on the virus reservoir. However, even if engineered antibodies
can be a significant improvement over wild type molecules, they will likely need to be used in combination
with other immune-based interventions, such as therapeutic vaccines, to overcome the limitations of
monotherapies and exert a significant impact on the viral reservoir. The proposed studies will determine
whether the combination of a therapeutic vaccine based on an integrase defective lentiviral vector (IDLV)
and a cocktail of Fc-engineered bnAbs (e-bnAbs) could be a strategy to induce durable virologic control
and reservoir size reduction. Our prior work has demonstrated that IDLV can drive prolonged transgene
expression and durable immune responses following intramuscular injection. In preliminary data, we
show that a single immunization with an IDLV-Gag therapeutic vaccine was effective at enhancing anti-
Gag CD8+ T cell responses in chronically SHIV infected macaques and resulted in durable suppression
of virus replication in absence of ART. We propose to further improve the IDLV platform by assessing
the impact that modulation of transgene expression levels, in both dendritic cells and muscle cells, have
on the resulting immune responses (Aim 1). We will perform pharmacokinetics studies in transgenic mice
expressing the human Fc receptor (FcRn) to determine the half-lives and effector functions of
combinations of bnAbs that have been engineered (e-bnAbs) to improve their half-lives and effector
functions (Aim 2). We will assess the impact that the combination of the cocktail of e-bnAbs and the
improved IDLV therapeutic vaccine have on viral load and reservoir size in efficacy studies in SHIV-
infected macaques (Aim 3). Collectively, results from this work will provide valuable information for the
design of therapeutic strategies against the HIV-1 reservoir.

## Key facts

- **NIH application ID:** 10240365
- **Project number:** 1R56AI150359-01A1
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Maria Blasi
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $760,086
- **Award type:** 1
- **Project period:** 2020-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10240365

## Citation

> US National Institutes of Health, RePORTER application 10240365, Targeting the HIV-1 reservoir with a combination of an IDLV-SIVGag therapeutic vaccine and Fc-engineered bnAbs (1R56AI150359-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10240365. Licensed CC0.

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