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Rescue of Recombinant Newcastle Disease Virus from cDNA
Published on: October 11, 2013
Protection against respiratory syncytial virus by a recombinant Newcastle disease virus vector
Luis Martinez-Sobrido1, Negin Gitiban, Ana Fernandez-Sesma
1Columbus Children's Research Institute, 700 Children's Drive, WA-4104, Columbus, OH 43205, USA.
Insights
Developing a novel vaccine using Newcastle disease virus (NDV) expressing the respiratory syncytial virus (RSV) fusion glycoprotein protected mice from RSV challenge. This approach overcomes RSV
Area of Science:
- Virology
- Immunology
- Vaccinology
Background:
- Respiratory syncytial virus (RSV) causes severe lower respiratory tract disease, particularly in infants and the elderly.
- Current RSV vaccines are lacking due to the virus's weak immunogenicity and historical vaccine-induced immunopathology.
- RSV poorly stimulates innate immunity, complicating the development of effective adaptive immune responses.
Purpose of the Study:
- To investigate if expressing the RSV fusion glycoprotein via Newcastle disease virus (NDV) could elicit a stronger immune response than natural RSV infection.
- To test the hypothesis that weak innate immune stimulation by RSV correlates with ineffective adaptive immunity.
Main Methods:
- A recombinant NDV was engineered to express the RSV fusion glycoprotein.
- This recombinant NDV was administered to BALB/c mice.
- Mice were subsequently challenged with RSV to assess protection and immune responses.
Main Results:
- Mice vaccinated with the recombinant NDV were protected against RSV challenge.
- Protection correlated with a robust CD8+ T-cell response targeting the RSV fusion (F) protein.
- The vaccine's effectiveness was linked to NDV's superior ability to induce dendritic cell maturation compared to RSV.
Conclusions:
- Newcastle disease virus (NDV) expressing the RSV fusion glycoprotein can induce protective immunity against RSV.
- The enhanced immunogenicity is attributed to NDV's potent induction of innate immune responses, specifically dendritic cell maturation.
- This vaccine strategy shows promise even without a functional interferon-alpha/beta receptor, suggesting broad applicability.
Abstract:
Respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract disease in infants and the elderly, but no safe and effective RSV vaccine is yet available. For reasons that are not well understood, RSV is only weakly immunogenic, and reinfection occurs throughout life. This has complicated the search for an effective live attenuated viral vaccine, and past trials with inactivated virus preparations have led to enhanced immunopathology following natural infection. We have tested the hypothesis that weak stimulation of innate immunity by RSV correlates with ineffective adaptive responses by asking whether expression of the fusion glycoprotein of RSV by Newcastle disease virus (NDV) would stimulate a more robust immune response to RSV than primary RSV infection. NDV is a potent inducer of both alpha/beta interferon (IFN-alpha/beta) production and dendritic cell maturation, while RSV is not. When a recombinant NDV expressing the RSV fusion glycoprotein was administered to BALB/c mice, they were protected from RSV challenge, and this protection correlated with a robust anti-F CD8+ T-cell response. The effectiveness of this vaccine construct reflects the differential abilities of NDV and RSV to promote dendritic cell maturation and is retained even in the absence of a functional IFN-alpha/beta receptor.
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