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 in the elderly and immunocompromised populations. No approved RSV vaccine exists. Our goal is to define broadly protecting antibody epitopes on RSV G protein. RSV G protein is one of two major immunogenic proteins on the RSV surface and plays key roles in virus attachment to airway epithelial cells and virus modulation of innate immune defenses. Despite the important role of RSV G protein in infection and pathogenesis, little is known about the structural and molecular features that govern its activities. Our central hypothesis is that the central conserved region of RSV G protein contains both linear and conformational epitopes for broadly protecting antibodies. Using an integrated structural and biophysical approach, we will pursue two specific aims to (1) Identify RSV G protein constructs that maintain high-affinity binding to anti-G antibodies and (2) Use structural studies to define epitopes on RSV G protein recognized by broadly protecting antibodies. Results obtained by this work will provide a molecular roadmap for the development of novel RSV G vaccine immunogens to prevent RSV infection and disease.

Public Health Relevance

Respiratory syncytial virus is the top cause of severe lower respiratory tract disease in young children worldwide. This proposal seeks to understand at the molecular level how antibodies block virus infectivity and decrease disease. These findings will be important for understanding key vulnerabilities of the virus and developing a vaccine to prevent RSV disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI130605-02
Application #
9607983
Study Section
Virology - A Study Section (VIRA)
Program Officer
Kim, Sonnie
Project Start
2017-12-05
Project End
2019-11-30
Budget Start
2018-12-01
Budget End
2019-11-30
Support Year
2
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of California Santa Cruz
Department
Engineering (All Types)
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
125084723
City
Santa Cruz
State
CA
Country
United States
Zip Code
95064
Fedechkin, Stanislav O; George, Natasha L; Wolff, Jacob T et al. (2018) Structures of respiratory syncytial virus G antigen bound to broadly neutralizing antibodies. Sci Immunol 3: