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.

  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 #
1ZIAAI005061-13
Application #
9161765
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
13
Fiscal Year
2015
Total Cost
Indirect Cost

  Institution

Name
Niaid Extramural Activities
Department
Type
DUNS #
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  Publications

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:
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
Graham, Barney S; Modjarrad, Kayvon; McLellan, Jason S (2015) Novel antigens for RSV vaccines. Curr Opin Immunol 35:30-8
Kines, Rhonda C; Zarnitsyn, Vladimir; Johnson, Teresa R et al. (2015) Vaccination with human papillomavirus pseudovirus-encapsidated plasmids targeted to skin using microneedles. PLoS One 10:e0120797
Correia, Bruno E; Bates, John T; Loomis, Rebecca J et al. (2014) Proof of principle for epitope-focused vaccine design. Nature 507:201-6
Johnson, Teresa R; Rangel, David; Graham, Barney S et al. (2014) Genetic vaccine for respiratory syncytial virus provides protection without disease potentiation. Mol Ther 22:196-205
McLellan, Jason S; Chen, Man; Leung, Sherman et al. (2013) Structure of RSV fusion glycoprotein trimer bound to a prefusion-specific neutralizing antibody. Science 340:1113-7
Graham, Barney S (2013) Advances in antiviral vaccine development. Immunol Rev 255:230-42
McLellan, Jason S; Chen, Man; Joyce, M Gordon et al. (2013) Structure-based design of a fusion glycoprotein vaccine for respiratory syncytial virus. Science 342:592-8
Graham, Barney S; Anderson, Larry J (2013) Challenges and opportunities for respiratory syncytial virus vaccines. Curr Top Microbiol Immunol 372:391-404

Showing the most recent 10 out of 18 publications