# Structure-guided engineering to increase respiratory syncytial virus G protein immunogenicity

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA SANTA CRUZ · 2023 · $754,322

## Abstract

PROJECT SUMMARY
Respiratory syncytial virus (RSV) is the leading cause of severe lower respiratory tract disease in young
children worldwide and is also a major cause of morbidity and some mortality in the elderly and
immunocompromised. No approved RSV vaccine exists. Our goal is to utilize a structure-guided design
approach to rationally engineer RSV G protein immunogens that induce robust and protective immunity against
RSV. RSV G protein is one of two major immunogenic proteins on the RSV surface and has key roles in virus
attachment to airway epithelial cells and virus modulation of innate immune defenses. RSV G protein is the
target of neutralizing and protective antibodies. The G protein as a vaccine immunogen has been hampered by
poor immunogenicity and by a paucity of structural information on its epitopes. In this proposal, we will test our
central hypothesis that engineered multimeric RSV G immunogens that display protective conformational
epitopes will elicit robust and protective RSV immunity. We will use an integrated approach to pursue four
specific aims: (1) Use structural studies to define conserved RSV G protein epitopes recognized by protective
antibodies, (2) Use structure-guided design to engineer multimeric RSV G protein immunogens, (3) Evaluate
engineered RSV G protein immunogens for improved immunogenicity, and (4) Use a comprehensive immune
analysis to evaluate RSV G protein CCD immunogens for balanced cytokine responses and protective
antibodies made in response to vaccination. The proposed research will generate RSV G vaccine immunogens
as candidates with demonstrated efficacy in preventing RSV infection and disease pathogenesis.

## Key facts

- **NIH application ID:** 10624413
- **Project number:** 5R01AI166066-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA SANTA CRUZ
- **Principal Investigator:** Rebecca Michelle DuBois
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $754,322
- **Award type:** 5
- **Project period:** 2022-05-19 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10624413

## Citation

> US National Institutes of Health, RePORTER application 10624413, Structure-guided engineering to increase respiratory syncytial virus G protein immunogenicity (5R01AI166066-02). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10624413. Licensed CC0.

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