The long-term objective of this proposal is to obtain safe and effective vaccines for the prevention of the most common respiratory viruses of childhood, namely respiratory syncytial virus and human parainfluenza viruses, type 1 and 3. In spite of their epidemiologic importance, no vaccines exist for these pathogens. In this program it is proposed that the murine type 1 parainfluenza virus, Sendai virus, is an effective vaccine for its human cognate (human parainfluenza virus type 1; hPIV1). Based on our previous demonstration of SV-induced protection against hPIV1 in non-human primates and preliminary success in manipulating the cDNA of SV obtained through reverse genetics, we propose that SV can serve as an effective vaccine for hPIV1 and as a vaccine backbone for additional paramyxoviral antigens. The Paramyxovirus Vaccine Program at SJCRH integrates pre-clinical and clinical research and involves members of the Departments of Infectious Diseases, the Division of Virology and the Department of Immunology. This integrated, multidisciplinary approach is essential to ultimately determine the immunologic and virologic features that reliably predict paramyxovirus vaccine efficacy. The Program consists of 3 Projects: Project 1 - Recombinant Sendai virus as a novel paramyxovirus vaccine (PORTNER); Project 2 - Immune response and vaccine efficacy in a rodent model (HURWITZ); and Project 3 - Clinical and primate paramyxovirus vaccine evaluation (SLOBOD). The strengths of the Program are based in the strength of Sendai virus as a vaccine backbone and in the experience, skills and diversity of the assembled investigators working together towards a unified objective. Ultimately, this program will yield (1) a candidate respiratory virus vaccine; (2) reagents including a panel of 12 recombinant Sendai virus vaccines (differing according to target gene identity and mode of expression), monoclonal antibodies, purified recombinant proteins of hPIV-3 and RSV; and (3) information which can be applied to the study of paramyxovirus vaccine development, including T and B cell studies of durable immunity to these most common respiratory viruses. Taken together, this comprehensive program has a high likelihood of success, measured as the identification of protective and safe respiratory virus vaccines.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program Projects (P01)
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Microbiology and Infectious Diseases B Subcommittee (MID)
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Kim, Sonnie
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St. Jude Children's Research Hospital
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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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