Abstract

RSV presents a significant cause of morbidity in the very young and elderly and there is currently no licensed vaccine to prevent RSV infection. The induction of both protective, disease-sparing CD8+ T cell responses and protective neutralizing antibodies are desirable in a vaccine candidate. 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. We have characterized numerous gene-based delivery vectors that express the wild-type RSV F protein. In another project Antigenicity and Immunogenicity of Stablized prefusion F protein, we have stabilized the RSV F protein in the prefusion conformation (Pre-F) and characterized the antigenicity and immunogenicity of the Pre-F protein. Currently, we are comparing vaccine regimens using DNA plasmids and gorilla adenovirus vectors expressing either the stabilized Pre-F protein or the wildtype F protein to vaccination with soluble Pre-F protein.

  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 #
1ZIAAI005061-14
Application #
9360469
Study Section
Project Start
Project End
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Budget End
Support Year
14
Fiscal Year
2016
Total Cost
Indirect Cost

  Institution

Name
Niaid Extramural Activities
Department
Type
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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

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