Abstract

Immunogens inducing protective, disease-sparing CD8+ T cell responses are a primary focus of research efforts at the VRC. These studies are designed to identify interventions that will increase the efficiency of nucleic acid and vector-based immunization and to optimize the conditions of each intervention. The magnitude and the quality of the immune responses induced by each vector will be compared using murine prime-challenge models. The RSV F glycoprotein is a key target for vaccine-induced neutralizing antibody. Our hypothesis is that understanding the mechanism of antibody neutralization will be facilitated by defining the structure of F and the structure of epitopes associated with neutralization. This will allow novel antigen design. Characterizing the chemistry and post-translational modifications in F will also promote improved vaccine antigen design. We have advanced our stabilized prefusion F protein into clinical evaluation in a Phase 1 clinical trial, VRC 317. In this trial, we are evaluating safety, tolerability, and immunogenicity of our stabilized prefusion F protein (DS-Cav1) with or with alum adjuvant in healthy adults.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAI005129-02
Application #
9551287
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2017
Total Cost
Indirect Cost

  Institution

Name
Niaid Extramural Activities
Department
Type
DUNS #
City
State
Country
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  Publications

Graham, Barney S (2017) Vaccine development for respiratory syncytial virus. Curr Opin Virol 23:107-112
Leemans, A; De Schryver, M; Van der Gucht, W et al. (2017) Antibody-Induced Internalization of the Human Respiratory Syncytial Virus Fusion Protein. J Virol 91:
Liang, Bo; Ngwuta, Joan O; Surman, Sonja et al. (2017) Improved Prefusion Stability, Optimized Codon Usage, and Augmented Virion Packaging Enhance the Immunogenicity of Respiratory Syncytial Virus Fusion Protein in a Vectored-Vaccine Candidate. J Virol 91:
Zhao, Min; Zheng, Zi-Zheng; Chen, Man et al. (2017) Discovery of a Prefusion Respiratory Syncytial Virus F-Specific Monoclonal Antibody That Provides Greater In Vivo Protection than the Murine Precursor of Palivizumab. J Virol 91:
Graham, Barney S (2016) Vaccines against respiratory syncytial virus: The time has finally come. Vaccine 34:3535-41
Liang, Bo; Ngwuta, Joan O; Herbert, Richard et al. (2016) Packaging and Prefusion Stabilization Separately and Additively Increase the Quantity and Quality of Respiratory Syncytial Virus (RSV)-Neutralizing Antibodies Induced by an RSV Fusion Protein Expressed by a Parainfluenza Virus Vector. J Virol 90:10022-10038
Boyington, Jeffrey C; Joyce, M Gordon; Sastry, Mallika et al. (2016) Structure-Based Design of Head-Only Fusion Glycoprotein Immunogens for Respiratory Syncytial Virus. PLoS One 11:e0159709
Joyce, M Gordon; Zhang, Baoshan; Ou, Li et al. (2016) Iterative structure-based improvement of a fusion-glycoprotein vaccine against RSV. Nat Struct Mol Biol 23:811-820
Francica, Joseph R; Lynn, Geoffrey M; Laga, Richard et al. (2016) Thermoresponsive Polymer Nanoparticles Co-deliver RSV F Trimers with a TLR-7/8 Adjuvant. Bioconjug Chem 27:2372-2385
Graham, Barney S; Modjarrad, Kayvon; McLellan, Jason S (2015) Novel antigens for RSV vaccines. Curr Opin Immunol 35:30-8

Showing the most recent 10 out of 11 publications