# AAV Vectored Delivery of Broadly Neutralizing Antibodies with Optimal Innate Functionality Against HIV

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $781,279

## Abstract

Project Summary / Abstract
 This proposal describes the framework of an R01 grant for Alejandro Balazs, PhD. Dr. Balazs is
currently an assistant professor at Harvard Medical School working as a principal investigator at the Ragon
Institute of MGH, MIT & Harvard. Dr. Balazs’ research is focused on engineering the immune system via gene
transfer as a novel means of creating protection against HIV. Broadly neutralizing antibodies (bNAbs) against
human immunodeficiency virus (HIV) show great promise in HIV prevention and therapy as they potently
neutralize a significant breadth of globally circulating HIV strains. A number of animal experiments and clinical
trials have demonstrated the ability of bNAbs to confer protection from viral challenge and reduce viremia of
established infections. BNAbs can inhibit HIV infection by blocking viral attachment or membrane fusion;
however, recent work suggests that the fragment crystallizable (Fc) region of antibodies may also contribute
significantly to bNAb-mediated HIV inhibition through interactions with innate immunity. This proposal seeks to
use in vitro cell-based assays to determine the extent to which next-generation HIV bNAbs engage effector
functions, such as antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular
phagocytosis (ADCP). This proposal will modify the Vectored ImmunoProphylaxis technology pioneered by Dr.
Balazs to generate sustained expression of antibodies harboring precise Fc-region mutations previously
demonstrated to enhance or abrogate, Fc-receptor interactions. By manipulating the specificity and
concentration of these antibodies, this study will define the rules governing Fc-receptor engagement that apply
to prevention of HIV acquisition. Furthermore, it seeks to determine the potential for Fc-enhanced antibodies to
increase the potency of bNAb protection against HIV transmission. Finally, this proposal will manipulate the
immune system of humanized mice as a means of dissecting and precisely quantifying the contribution of
specific immune cells to prevention of HIV transmission. Together, this work will reveal optimal epitope targets
and innate immune mechanisms to produce next-generation AAV vectors encoding bNAbs with enhanced
innate immune function to prevent HIV transmission.

## Key facts

- **NIH application ID:** 10868521
- **Project number:** 5R01AI174875-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Alejandro Benjamin Balazs
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $781,279
- **Award type:** 5
- **Project period:** 2023-06-15 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10868521

## Citation

> US National Institutes of Health, RePORTER application 10868521, AAV Vectored Delivery of Broadly Neutralizing Antibodies with Optimal Innate Functionality Against HIV (5R01AI174875-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10868521. Licensed CC0.

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