# Eliminating the Immunogenicity of AAV Vectored HIV Antibody Delivery

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $822,056

## 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. Two recent Phase I clinical studies have
demonstrated the safety and potential for adeno associated virus (AAV) vectors to deliver bNAbs to human
participants following intramuscular injection. These have resulted in markedly different outcomes: A lack of
expression and significant immunogenicity from AAV1-PG9, or long-lived expression and less immunogenicity
from AAV8-VRC07. The mechanisms underlying these differences are poorly defined. This proposal will
uncover the elements of vectored immunoprophylaxis which are responsible for the immunogenicity seen in
human trials. It will dissect the immunological response during vector administration in patients at single-cell
resolution using multi-modal approaches. It will engineer novel AAV capsids designed to avoid stimulating the
immune system through directed evolution to avoid antigen presenting cells. Furthermore, it will test the
functional capacity of next-generation antibodies delivered by novel AAV capsids in animal models of
sustained virologic remission and evaluate the immune response to novel capsid designs. Together this work
will greatly enhance our understanding of the human immune response to AAV vectors and yield capsids that
eliminate the development of transgene immunogenicity to enable the use of vectored antibody delivery for HIV
cure strategies.

## Key facts

- **NIH application ID:** 10811991
- **Project number:** 1R01AI174276-01A1
- **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:** $822,056
- **Award type:** 1
- **Project period:** 2024-01-08 → 2028-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10811991

## Citation

> US National Institutes of Health, RePORTER application 10811991, Eliminating the Immunogenicity of AAV Vectored HIV Antibody Delivery (1R01AI174276-01A1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10811991. Licensed CC0.

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