A Novel Approach to RSV Vaccination


Principal Investigator: Joan E Durbin
Abstract: Respiratory syncytial virus (RSV) is a paramyxovirus that infects essentially all persons by their second birthday. Infants experiencing their first infection are most susceptible to lower airway infection in the form of bronchiolitis and pneumonia, but older adults and immunocompromised patients also experience severe RSV disease. In addition, this virus frequently reinfects healthy, immunocompetent individuals throughout life. Disease in seropositive adults and older children is usually limited to the upper airway, but significant virus shedding has been observed at each reinfection thus maintaining the virus within an immune population. The reason for this relatively ineffective immune response to RSV infection is not well understood, but the poor immunogenicity of this pathogen has so far confounded attempts to develop a safe and effective RSV vaccine. Currently there is no treatment for RSV, only transient prophylaxis in the form of a humanized monoclonal antibody targeting the RSV F protein. In a new approach to RSV vaccine design we made use of a viral vector derived from an avian paramyxovirus, Newcastle disease virus (NDV), chosen because it is known to be a very strong trigger for IFN-α/βproduction in mammalian species As expected, intranasal instillation of recombinant NDV encoding the RSV F gene (NDV-F) into mice induced 1000 times more IFN-α/βthan did an equivalent dose of RSV, and 3 weeks after NDV-F priming mice were protected from live virus challenge. In addition, as we had hoped, NDV-F priming elicited significantly more RSV F protein-specific memory CD8+ T cells than did RSV itself. This result has now been reproduced in two additional rodent species (chinchillas and cotton rats).To test the NDV-F vaccine candidate for safety, efficacy, and establishment of long-lived protection we propose the following aims: 1) Generation of an optimized NDV-F vaccine candidate. 2) Assessment of T and B cell responses to the HRSV F protein following NDV-F priming, protection from live virus challenge, histopathology, and immunological memory in the cotton rat. 3) Assessment of T and B cell responses to the BRSV F protein following NDV-FB priming, protection from live virus challenge, histopathology, and immunological memory in the cow. 4) Large scale production of genetically stable NDV-F under GMP conditions.
Funding Period: 2013-08-16 - 2015-08-15
more information: NIH RePORT

Top Publications

  1. pmc Novel vaccine strategies against emerging viruses
    Adolfo Garcia-Sastre
    Department of Microbiology, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, United States
    Curr Opin Virol 3:210-6. 2013

Detail Information


  1. pmc Novel vaccine strategies against emerging viruses
    Adolfo Garcia-Sastre
    Department of Microbiology, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, United States
    Curr Opin Virol 3:210-6. 2013
    ..These approaches might be applied to the control of many other emerging pathogens...

Research Grants30

  1. The Shelf Live Evaluation of Investigational Dosage Forms
    Jonathan White; Fiscal Year: 2013
    ..This contract is essential for continued assurance of the quality of drugs undergoing clinical investigation for different types of cancer by Cancer Therapeutics Evaluation Program. ..
  2. New England Regional Center of Excellence in Biodefense and Emerging Infectious D
    Dennis L Kasper; Fiscal Year: 2013
    ..NERCE will also continue its Developmental Projects program and Career Development in Biodefense program in an effort to initiate new research efforts and to attract new investigators to this field. ..
  3. Northeast Biodefense Center
    W Ian Lipkin; Fiscal Year: 2013
    ..As a Center based in a School of Public Health and a State Department of Health, the NBC has a firm commitment to and practical understanding of Emergency Preparedness. ..
  4. Optimization of HIV vaccines for the induction of cross-reactive antibodies
    Shan Lu; Fiscal Year: 2013
    ..RELEVANCE: To optimize the next generation polyvalent Env HIV vaccine formulations using the multi-gene, polyvalent DNA prime - protein boost technology platform. ..
  5. Shaping Antiviral Immunity by the Inflammatory, Regulatory and Tissue Environment
    E John Wherry; Fiscal Year: 2013
    ..Our goal is to define how unrelated infections impact immunological memory in hopes to improve vaccines. ..
  6. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery
    Dennis R Burton; Fiscal Year: 2013
    ..The team will be sustained by five Scientific Research Support Components (SRSCs), including strong Operations and Management, that have been assembled to maximally accelerate progress toward the designated goals. ..
  7. A Mucosal RSV Vaccine
    Kejian Yang; Fiscal Year: 2013
  8. Mentoring Research Excellence in Aging and Regenerative Medicine
    S Michal Jazwinski; Fiscal Year: 2013
    ..This COBRE will represent the centerpiece of the Tulane Center for Aging, and it will contribute strongly to our building of an exceptional biomedical aging research enterprise in Louisiana. ..
  9. Center for Narcolepsy and Related Disorders (P50)
    Emmanuel J Mignot; Fiscal Year: 2013
    ..We also want to understand why the immune system destroys hypocretin neurons in narcolepsy and to prevent/cure it. ..
  10. Primary Immune Deficiency Treatment Consortium
    Morton Cowan; Fiscal Year: 2013
    ..These studies will resolve critical questions concerning HCT for these disorders and form the basis for future prospective clinical trials. ..
  11. Cellular &Molecular Defects in Human B Cell Development
    Charlotte Cunningham-Rundles; Fiscal Year: 2013
    ..We hypothesize that mutations in this receptor and its isoforms can be used to elucidate the complex functions of this receptor in a human system. ..
  12. Caloric Restricted Rodent Colony
    RICK MORIN; Fiscal Year: 2013
    ..The purpose of this project is to develop, maintain and distribute a standing colony ofaged, calorically restricted rodents ofdefined strains for use by investigators in studies of aging. ..
  13. Novel Ad/MVA and Ad/Protein HIV-1 Vaccines
    Dan H Barouch; Fiscal Year: 2013
    ..To define the mechanism of blocking acquisition of stringent SIV challenges by conducting antigen formulation and adoptive transfer studies in rhesus monkeys. ..
  14. Immune Regulation of Virus Clearance and Tissue Injury at Sites of Infection
    Thomas J Braciale; Fiscal Year: 2013
    ..To determine the impact of viral infection on the production of Te-derived IL- 10. The proposed studies are designed to complement ongoing related studies in Projects 2, 3 and 4. ..
  15. The Role of TLR4 and RSV F Protein in Immunity to RSV
    JORGE C BLANCO; Fiscal Year: 2013
    ..It is expected that at the completion of this grant, we will have identified strategies that may lead to development of a RSV vaccine and new therapeutics for mitigating the pathologic host response to RSV. ..
  16. Oxidation in Inflammation and Cardiovascular Disease
    Stanley L Hazen; Fiscal Year: 2013
    ..It may also lead to important insights for atherosclerosis risk assessment, diagnosis and therapy. ..
  17. Endothelial Injury and Repair: CardioPulmonary Vascular Biology COBRE
    SHARON IRENE SMITH ROUNDS; Fiscal Year: 2013
    ..abstract_text> ..
  18. Pacific NorthWest Regional Center of Excellence (PNWRCE)
    Jay A Nelson; Fiscal Year: 2013
    ..pseudomallei host pathogen response during both the septicemic as well as the intracellular phases of the disease. ..
  19. Southeast Regional Centers of Excellence for Biodefense &Emerging Infectious Di
    Philip Frederick Sparling; Fiscal Year: 2013
    ..SERCEB brings new investigators to the biodefense effort through a combination of educational programs, support of innovative new projects, and the synergistic interactions among its world-class investigators. ..
  20. Pacific Southwest RCE for Biodefense &Emerging Infectious Diseases Research
    Alan G Barbour; Fiscal Year: 2013
    ..abstract_text> ..
  21. Optimizing HIV immunogen-BCR interactions for vaccine development
    LEONIDAS A STAMATATOS; Fiscal Year: 2013
  22. Harnessing Human DC Subsets for Improved Muscosal Vaccines
    Gerard Zurawski; Fiscal Year: 2013
    ..We propose four projects and two technical development components which will be supported by six cores. ..
  23. Adenovirus-vectored RSV vaccine not inhibited by maternal immunity
    JASON GRAHAM GALL; Fiscal Year: 2013
    ..In phase I we will test the hypothesis that RSV-specific immune responses induced by a novel replication-deficient adenovirus vector derived from non-human adenovirus will not be inhibited by human viral immunity. ..
  24. Rocky Mountain Regional Center of Excellence or Biodefense and Emerging Infectiou
    John T Belisle; Fiscal Year: 2013
    ..abstract_text> ..
    Rafi Ahmed; Fiscal Year: 2013