There is currently no vaccine or standard treatment for RSV. However there is clearly an unmet medical need: RSV is responsible for approximately 100,000 hospitalizations per year in the U.S. alone, and is globally responsible for more than 150,000 deaths per year. The continued absence of vaccines and standard treatments for RSV disease represents an important and serious gap in preventive medicine. In response to RFA AI-09-016, investigators from St. Jude Children's Research Hospital, Novartis Vaccines and Diagnostics, Inc., and Le Bonheur Children's Medical Center are proposing a partnership to expedite RSV vaccine development. Recombinant murine Sendai virus (SeV) expressing RSV F glycoprotein (rSeV-RSV-F) is an extremely attractive candidate for an RSV vaccine. This xenotropic vaccine elicits rapid and durable protection against RSV in an animal model and is associated with no enhanced immunopathology upon RSV infection. Since an RSV vaccine will need to protect infants, and since maternal antibodies can reduce the efficacy of replicating and non-replicating vaccines, fundamental questions concerning vaccine-antibody interactions must be addressed prior to clinical development of rSeV-RSV-F. Our Central Hypothesis is that the rSeV-RSV-F vaccine will confer RSV protection to infants, even in the presence of maternal antibodies.
Our Specific Aims are: (1) To determine the relative functional titers of anti-SeV (PIV1) and anti-RSV antibodies in human infants, (2) To determine the influence of maternal antibodies on rSeV-RSV-F vaccine efficacy (in a cotton rat model), and (3) To optimize vaccine by formulation and regimen. When optimized vaccine doses/formulations/regimens are identified, these will be further tested: (i) to ensure the absence of enhanced immunopathology, (ii) to measure response durability, and (iii) to measure immune correlates of protection. Data from these experiments will have broad application to the pediatric vaccine field, and will be critical to the launch of clinical trials with rSeV-RSV-F.
Despite decades of work, no successful RSV vaccine has yet been developed. The long-term objectives of our research is to develop an RSV vaccine to prevent RSV- induced morbidity and mortality in humans.
|Surman, Sherri L; Jones, Bart G; Woodland, David L et al. (2017) Enhanced CD103 Expression and Reduced Frequencies of Virus-Specific CD8+ T Cells Among Airway Lymphocytes After Influenza Vaccination of Mice Deficient in Vitamins A?+?D. Viral Immunol 30:737-743|
|Penkert, Rhiannon R; Jones, Bart G; Häcker, Hans et al. (2017) Vitamin A differentially regulates cytokine expression in respiratory epithelial and macrophage cell lines. Cytokine 91:1-5|
|Penkert, Rhiannon R; Iverson, Amy; Rosch, Jason W et al. (2017) Prevnar-13 vaccine failure in a mouse model for vitamin A deficiency. Vaccine 35:6264-6268|
|Sealy, Robert E; Surman, Sherri L; Hurwitz, Julia L (2017) CD4+ T cells support establishment of RSV-specific IgG and IgA antibody secreting cells in the upper and lower murine respiratory tract following RSV infection. Vaccine 35:2617-2621|
|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|
|Penkert, Rhiannon R; Surman, Sherri L; Jones, Bart G et al. (2016) Vitamin A deficient mice exhibit increased viral antigens and enhanced cytokine/chemokine production in nasal tissues following respiratory virus infection despite the presence of FoxP3+ T cells. Int Immunol 28:139-52|
|Meliopoulos, Victoria A; Van de Velde, Lee-Ann; Van de Velde, Nicholas C et al. (2016) An Epithelial Integrin Regulates the Amplitude of Protective Lung Interferon Responses against Multiple Respiratory Pathogens. PLoS Pathog 12:e1005804|
|Jones, Bart G; Penkert, Rhiannon R; Xu, Beisi et al. (2016) Binding of estrogen receptors to switch sites and regulatory elements in the immunoglobulin heavy chain locus of activated B cells suggests a direct influence of estrogen on antibody expression. Mol Immunol 77:97-102|
|Sealy, Robert E; Surman, Sherri L; Vogel, Peter et al. (2016) Antibody-secreting cells in respiratory tract tissues in the absence of eosinophils as supportive partners. Int Immunol 28:559-564|
|Hankins, Jane S; Penkert, Rhiannon R; Lavoie, Paul et al. (2016) Original Research: Parvovirus B19 infection in children with sickle cell disease in the hydroxyurea era. Exp Biol Med (Maywood) 241:749-54|
Showing the most recent 10 out of 33 publications