# Neutralization of Primate Immunodeficiency Viruses

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2020 · $273,001

## Abstract

Project Summary. There remains a critical need to stop the spread of HIV-1, which still infects 6000
persons per day worldwide, and better therapies to treat or even cure established infections would be
beneficial. Broadly neutralizing antibodies (bNAbs) are now being evaluated in passive immunization
for preventing and treating HIV-1 infection; and eliciting bNAbs is a central goal of multiple vaccine-
development efforts. All of these various translational programs will benefit from an expanded
mechanistic and quantitative knowledge of how neutralizing bNAbs act. There are many gaps in our
knowledge about how bNAbs interact with HIV-1 in vivo, in environments where neutralization in the
absence of activating Fc-receptor interactions is insufficient to potently prevent transmission or
suppress viremia. NAbs are traditionally evaluated for potency, but other, relatively neglected, aspects
of neutralization may also influence the outcome of Env vaccination and bNAb-based therapy.
Our long-term goal is to be able to identify bNAbs or combinations of bNAbs with optimal anti-viral
properties and thereby to minimize the risk of viral breakthrough and escape. Our overall objective is
to quantify and explain neglected aspects of HIV-1 neutralization that may improve the designs of
bNAb-based vaccination and therapy. Our central hypothesis is that the efficacy of neutralization (the
converse of persistent infectivity), the varying interactions between cells and virions, the mechanisms
and kinetics of how antibodies impede viral entry, and the propensity for escape together influence the
outcome of passive and active immunization. Our observations of markedly reduced maximum
neutralization plateaus for some HIV-1 strains when they are treated with certain NAbs or with sera
from trimer-immunized animals are pertinent to this hypothesis. In summary, by quantifying the
effects of NAbs on HIV-1 entry into different cells, and by exploring the conditions of viral escape, we
seek to complement simple measurements of neutralization potency and thereby build an explanatory
predictive model for how NAbs act in vivo. An emphasis will be to use, whenever justified, clinically
relevant bNAbs as key tools in our in vitro research, to maximize the translational potential of the new
knowledge we will generate.
To test our central hypothesis and thereby obtain our objectives we propose three Specific Aims:
1. To define the causes of the persistent fraction in HIV-1 neutralization.
2. To determine the dynamics of HIV-1 neutralization.
3. To explain neutralization escape mechanisms in vitro and in vivo.
We expect our studies to bridge gaps in knowledge of how bNAbs act in vitro and in vivo and hence
guide improvements to clinically relevant passive immunization and active vaccination programs.

## Key facts

- **NIH application ID:** 9910357
- **Project number:** 5R01AI036082-28
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** JOHN P MOORE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $273,001
- **Award type:** 5
- **Project period:** 1994-05-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9910357

## Citation

> US National Institutes of Health, RePORTER application 9910357, Neutralization of Primate Immunodeficiency Viruses (5R01AI036082-28). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9910357. Licensed CC0.

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