AI Article Synopsis

  • Dengue virus (DENV) infection poses a significant global health risk, potentially affecting billions, with no specific treatments available except for vaccines.
  • The tetravalent dengue vaccine from Sanofi Pasteur has shown effectiveness in trials and is approved for individuals over 9 years who have previously been infected.
  • Researchers used mass spectrometry and cryo-electron microscopy to analyze the maturity of the vaccine viruses, finding that most of them showed a mature phenotype, which is important for their biological effectiveness.

Article Abstract

Dengue virus (DENV) infection is a global health threat with the potential to affect at least 3.6 billion people living in areas of risk. No specific curative treatments against dengue disease are available and vaccines are currently the only way to prevent the disease. The tetravalent dengue vaccine developed by Sanofi Pasteur has demonstrated significant efficacy in phase III studies and is now licensed in several countries for the prevention of disease in dengue-seropositives over 9 years of age. The vaccine is composed of four recombinant, live, attenuated vaccines (CYD 1-4) based on a yellow fever vaccine 17D (YFV 17D) backbone, each expressing the pre-membrane (prM) and envelope (E) genes of one of the four DENV serotypes. Virus maturity could impact the biological activity of the vaccine viruses. To address this question, the maturity of the four vaccine viruses used in phase III clinical studies was assessed by two complementary techniques: mass spectrometry (MS) and cryo-electron microscopy (cryoEM). MS assessed viral maturity at the molecular level by quantifying specifically the prM, and M proteins. CryoEM provided information at the particle level, allowing visualizing the different phenotypes of viral particles: spiky (immature), smooth/bumpy (mature), and mixed (partially mature). Results of the two assays used in this study show that all four CYD dengue vaccine viruses present in lots used in phase III efficacy trials, display in the majority a mature phenotype.

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Source
http://dx.doi.org/10.1016/j.vaccine.2019.05.012DOI Listing

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