# Assessing ADCC and Fc-mediated Protection against HIV

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $656,716

## Abstract

PROJECT SUMMARY
Efforts to develop an effective vaccine against HIV-1/AIDS continue to be hampered by an incomplete
understanding of the immune responses needed for protection. Non-neutralizing antibody functions, such as
the elimination of virus-infected cells by antibody-dependent cellular cytotoxicity (ADCC), are widely believed to
have contributed to the reduced risk of HIV-1 infection among vaccine recipients in the RV144 trial; however,
the antibody specificities and effector functions underlying this protection have not been clearly defined. This
uncertainty can be attributed in part to differences in methods for measuring ADCC, a limited understanding of
the factors influencing the sensitivity of HIV-infected cells to antibodies, and a lack of definitive evidence for
protection by non-neutralizing antibodies in animal models. Although correlative evidence suggests that
antibodies to variable 1 and 2 (V1V2) region and CD4-inducible (CD4i) epitopes of HIV-1 gp120 may have
contributed to protection, this has been difficult to confirm experimentally. The proposed studies will therefore
take advantage of the combined expertise of our research team to improve methods for measuring ADCC and
to test the antibody specificities and effector functions implicated in the outcome of the RV144 trial in a
nonhuman primate model. In Aim 1, we will determine the impact of viral and cellular factors that modulate the
sensitivity of HIV-infected cells to antibodies on methods for measuring ADCC. In Aim 2, we will develop and
implement a high-throughput assay platform to enable a comprehensive assessment of ADCC directed against
distinct conformations of the HIV-1 envelope glycoprotein. In Aim 3, we will test the hypothesis that V1V2-
and/or CD4i-specific antibodies can afford partial protection in a low-dose mucosal SHIV challenge model
designed to simulate conditions of HIV-1 CRF01_AE transmission in Thailand, where the RV144 trial took
place. In Aim 4, we will test Fc domain variants of V1V2- and CD4i-specific antibodies for the ability to protect
macaques against low-dose mucosal SHIV challenge to determine the extent to which Fc-mediated effector
functions may contribute to protection. These unprecedented studies are expected to reveal fundamental
molecular mechanisms that influence the sensitivity of HIV-infected cells to antibodies and their implications for
measuring ADCC, provide a standardizable, high-throughput assay for quantifying ADCC as a correlate of
protection, and yield greater insight into the types of antibody responses that may ultimately be needed for
protection against HIV-1.

## Key facts

- **NIH application ID:** 9994829
- **Project number:** 5R01AI148379-02
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** David T Evans
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $656,716
- **Award type:** 5
- **Project period:** 2019-08-13 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9994829

## Citation

> US National Institutes of Health, RePORTER application 9994829, Assessing ADCC and Fc-mediated Protection against HIV (5R01AI148379-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9994829. Licensed CC0.

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