# Structure-Based Designs of HIV-1 Immunogens Targeting Germline Precursors of Broadly Neutralizing Antibodies

> **NIH NIH R21** · FRED HUTCHINSON CANCER CENTER · 2022 · $220,000

## Abstract

PROJECT SUMMARY/ABSTRACT
Broadly neutralizing antibodies (bNAbs) are likely to be an important component of an HIV-1 vaccine. The HIV-
1 Envelope (Env) glycoprotein is the sole target of bNAbs and has been a focus of immunogen designs. Yet
diverse recombinant (rec) Envs do not display detectable binding to the inferred germline (gl) of certain bNAbs,
such as the VRC01-class bNAbs, which are the focus of this proposal. Rec Envs capable of binding glVRC01
bNAbs have been designed and induced the production of glVRC01 bNAbs when used as immunogens.
However, these novel immunogens are not sufficient to induce the maturation of glVRC01-class bNAbs to their
broad neutralization forms. Here we propose to use novel reagents as immunogens to guide the development
of VRC01-class bNAbs by: 1) immunizing knock-in mice with immunogens harboring short glycans to evaluate
if these could more efficiently prime immune responses that will accommodate the HIV-1 Env glycan shield and
2) combining immunological and biophysical (including atomic level structures) characterization. We
hypothesize that such immunogens will already know how to accommodate short glycans and thus be more
amenable to maturation. Our preliminary data show that such antigen has increased binding to precursors
glVRC01-like antibodies. The sequencing of monoclonal antibodies (mAbs) along with structural information
will provide molecular details on the interactions between the vaccine-elicited antibodies from animals and the
immunogens: better understanding the epitopes targeted by the novel vaccine-elicited mAbs will help us identify
the best boost immunogen for future immunizations studies and thus guide HIV-1 vaccine design.

## Key facts

- **NIH application ID:** 10374164
- **Project number:** 6R21AI157799-02
- **Recipient organization:** FRED HUTCHINSON CANCER CENTER
- **Principal Investigator:** Marie Pancera
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $220,000
- **Award type:** 6
- **Project period:** 2021-03-17 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10374164

## Citation

> US National Institutes of Health, RePORTER application 10374164, Structure-Based Designs of HIV-1 Immunogens Targeting Germline Precursors of Broadly Neutralizing Antibodies (6R21AI157799-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10374164. Licensed CC0.

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