Respiratory syncytial virus (RSV) and human parainfluenza viruses (hPIV) types 1 and 3 are the most common causes of acute viral respiratory disease in infants and young children. Currently, no safe and effective RSV or PIV vaccine has been developed for the prevention of these pathogens. The objective of the multi-project program is to develop a multivalent vaccine using novel Sendal virus recombinants (rSV), generated by reverse genetic techniques, to deliver critical antigens of RSV and hPIV-3 to the pediatric population. In addition, the SV backbone will provide immunity against hPIV-1 based on relatedness of these two type 1 parainfluenza viruses.
The Specific Aims of Project 1 descdbe our strategy to meet these objectives:
Specific Aim 1 : To construct and characterize a set of rSV expressing the envelope glycoproteins of hPIV-3 and RSV (types A and B), yielding a cocktail of first generation recombinants.
Specific Aim 2 : To compare the growth and target gene expression of rSV expressing membrane-bound versus secreted forms of the target glycoproteins of RSV and hPIV-3.
Specific Aim 3 : To prepare and characterize purified RSV and hPIV3 envelope glycoproteins, as a source of material for ELISA monitoring of antibody response and for possible boosting of rSV primed responses.This Project is highly related to the other two Projects in this application, rSV constructs, which differ according to the mode of the target antigen expression will be evaluated for immunogenicity by Project 2 investigators. Superior rSV will thus be selected and prepared in a formulation for the evaluation of safety and protection in a non-human primate model in Project 3. The combined Aims of Projects 1, 2 and 3 are intended to advance a SV-based respiratory virus vaccine to human trial for the prevention of serious respiratory virus infections in children.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
1P01AI054955-01A1
Application #
6735422
Study Section
Microbiology and Infectious Diseases B Subcommittee (MID)
Project Start
2003-12-01
Project End
2009-05-31
Budget Start
2004-06-01
Budget End
2005-05-31
Support Year
1
Fiscal Year
2004
Total Cost
$287,188
Indirect Cost
Name
St. Jude Children's Research Hospital
Department
Type
DUNS #
067717892
City
Memphis
State
TN
Country
United States
Zip Code
38105
Russell, Charles J; Jones, Bart G; Sealy, Robert E et al. (2017) A Sendai virus recombinant vaccine expressing a gene for truncated human metapneumovirus (hMPV) fusion protein protects cotton rats from hMPV challenge. Virology 509:60-66
Russell, Charles J; Hurwitz, Julia L (2016) Sendai virus as a backbone for vaccines against RSV and other human paramyxoviruses. Expert Rev Vaccines 15:189-200
Zhan, Xiaoyan; Slobod, Karen S; Jones, Bart G et al. (2015) Sendai virus recombinant vaccine expressing a secreted, unconstrained respiratory syncytial virus fusion protein protects against RSV in cotton rats. Int Immunol 27:229-36
Adderson, Elisabeth; Branum, Kristen; Sealy, Robert E et al. (2015) Safety and immunogenicity of an intranasal Sendai virus-based human parainfluenza virus type 1 vaccine in 3- to 6-year-old children. Clin Vaccine Immunol 22:298-303
Rudraraju, Rajeev; Sealy, Robert E; Surman, Sherri L et al. (2013) Non-random lymphocyte distribution among virus-infected cells of the respiratory tract. Viral Immunol 26:378-84
Rudraraju, Rajeev; Jones, Bart G; Sealy, Robert et al. (2013) Respiratory syncytial virus: current progress in vaccine development. Viruses 5:577-94
Jones, B G; Hayden, R T; Hurwitz, J L (2013) Inhibition of primary clinical isolates of human parainfluenza virus by DAS181 in cell culture and in a cotton rat model. Antiviral Res 100:562-6
Rudraraju, Rajeev; Surman, Sherri L; Jones, Bart G et al. (2012) Reduced frequencies and heightened CD103 expression among virus-induced CD8(+) T cells in the respiratory tract airways of vitamin A-deficient mice. Clin Vaccine Immunol 19:757-65
Jones, Bart G; Sealy, Robert E; Rudraraju, Rajeev et al. (2012) Sendai virus-based RSV vaccine protects African green monkeys from RSV infection. Vaccine 30:959-68
Rudraraju, Rajeev; Surman, Sherri; Jones, Bart et al. (2011) Phenotypes and functions of persistent Sendai virus-induced antibody forming cells and CD8+ T cells in diffuse nasal-associated lymphoid tissue typify lymphocyte responses of the gut. Virology 410:429-436

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