# High-resolution definition of B cell responses to HIV Env for immunogen design

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2020 · $796,104

## Abstract

Project Summary
The elicitation of broadly neutralizing antibodies (bNAbs) against HIV Env is one of the major
challenges of HIV-1 vaccine development. As a vaccine component, HIV-1 Env however elicits
limited neutralizing breadth and potency in most pre-clinical and clinical studies to date. The
isolation of second generation of bNAbs from HIV-infected individuals, and characterization
of their cognate epitopes on Env, offer a tremendous opportunity for understanding the
mechanisms underlying the elicitation of bNAb responses. As one of the most functionally
conserved and accessible elements of the HIV Env, the receptor binding site, namely CD4
binding site (CD4bs), plays a crucial role for virus engagement with receptor CD4 while serves
as a vulnerable target for bNAb response in natural infections. VRC01-class bNAbs, a subset
of CD4bs bNAbs isolated from donor 45 and numerous other HIV-infected individuals strongly
supports the premise of utilizing VRC01-class bNAbs as vaccine template. However, current
Env-based immunogens are not capable of eliciting potent VRC01-class bNAb response via
vaccination. The inferred VRC01- class bNAb germline precursors (gVRC01) often display
weak or no apparent affinity to prototypical Env immunogens. Thus, immunogen modifications
including approaches for efficiently activating, selectively expanding, and precisely shepherding
bNAb germline precursors (germline targeting) are needed for CD4bs bNAb elicitation, yet met
with limited success. During the last funding period, we established a panel of Env-based
designer immunogens with desirable antigenicity for eliciting CD4bs bNAb response. In this
proposal, we aim to extend our effort by an innovative program consisting of the following
three complementary specific aims: (1) to investigate the immunogenicity of novel
immunogens/regimens in bNAb germline BCR knockin mice; (2) to investigate the
immunogenicity of novel immunogens in guinea pigs and OmniMouse2 model that carries un-
rearranged human antibody loci; and (3) to explore a novel neutralizing epitope in the C3/V4
region of the Env as potential bNAb response target. We believe that through this study we will
(i) contribute to the thorough understanding of the basic aspects of the B cell response to the
HIV-1 Env following vaccination and natural infection; and (ii) contribute new immunogens,
new vaccine target, and optimized vaccination regimens leading to improved neutralizing
responses targeting conserved Env elements.

## Key facts

- **NIH application ID:** 9908031
- **Project number:** 5R01AI102766-08
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Yuxing Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $796,104
- **Award type:** 5
- **Project period:** 2013-01-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9908031

## Citation

> US National Institutes of Health, RePORTER application 9908031, High-resolution definition of B cell responses to HIV Env for immunogen design (5R01AI102766-08). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9908031. Licensed CC0.

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