# Monitoring the development of anti-Env Abs during HIV infection

> **NIH NIH R01** · FRED HUTCHINSON CANCER RESEARCH CENTER · 2020 · $645,753

## Abstract

   
DESCRIPTION (provided by applicant): This application aims at improving our understanding of the frequency and characteristics of naïve B cells that are the precursors of those that produce VRC01-class broadly neutralizing antibodies (bNAbs). VRC01-class bNAbs bind the CD4-binding site of the HIV Env and are among the most potent and broadly neutralizing antibodies known. They protect animals from experimental infection and when administered passively to chronically-infected patients they reduce plasma viremia. VRC01-like antibodies are therefore the type of antibodies one would want to elicit by vaccination. So far, however, this has not been achieved. We do know quite a few things about the mutated forms of VRC01-class antibodies, but there are many critical gaps in our knowledge of the germline form of these antibodies. Lab-engineered 'predicted' germline forms of such antibodies do not recognize Env. This information has led us and others to hypothesize that recombinant Envs fail to stimulate naïve B cells expressing germline VRC01-class B cell receptors (BCRs). However, the true nature of germline VRC01-class antibodies/BCRs is not known, so many of the assumptions we make about their infrequent elicitation during infection and their non-elicitation during immunization may be inaccurate. Here we will employ innovative and complementary methodologies and an interactive experimental approach to define the frequencies of naïve human B cells expressing germline VRC01-class BCRs, to define the true germline amino acid sequences of these antibodies/BCRs and to define their Env-recognition properties. The information gathered by our proposed studies will be critical to better understand how HIV-1 interacts with particular naïve B cells and also will be important for the design of Env-based immunogens capable of engaging the broadest possible array of germline VRC01-class BCRs.

## Key facts

- **NIH application ID:** 9851314
- **Project number:** 5R01AI081625-11
- **Recipient organization:** FRED HUTCHINSON CANCER RESEARCH CENTER
- **Principal Investigator:** Leonidas Stamatatos
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $645,753
- **Award type:** 5
- **Project period:** 2010-01-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9851314

## Citation

> US National Institutes of Health, RePORTER application 9851314, Monitoring the development of anti-Env Abs during HIV infection (5R01AI081625-11). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9851314. Licensed CC0.

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