Recombinant Chimeric Virus with Wild-Type Dengue 4 Virus Premembrane and Envelope and Virulent Yellow Fever Virus Asibi Backbone Sequences Is Dramatically Attenuated in Nonhuman Primates

McGee, Charles E.; Lewis, Mark G.; St. Claire, Marisa; Wagner, Wendeline; Lang, Jean; Guy, Bruno; Tsetsarkin, Konstantin; Higgs, Stephen; Decelle, Thierry
March 2008
Journal of Infectious Diseases;3/1/2008, Vol. 197 Issue 5, p693
Academic Journal
Candidate vaccine ChimeriVax viruses are attenuated, efficacious, safe, and highly unlikely to be transmitted by arthropod vectors. Nevertheless, concerns have been raised about the use of these vaccines because of the potential for recombination between vaccine and wild-type (WT) strains. To evaluate the vertebrate pathogenicity of such a worst-case recombinant, ChimeriVax-dengue (DEN) 4 virus was chimerized with the WT Asibi yellow fever virus. In this worst-case scenario, chimeric viruses remained fully attenuated in nonhuman primates. We therefore conclude that, even in the highly unlikely event of "virulent" backbone reversion, the safety of ChimeriVax-DEN vaccines would not be compromised.


Related Articles

  • Substitution of Wild-Type Yellow Fever Asibi Sequences for 17D Vaccine Sequences in ChimeriVax-Dengue 4 Does Not Enhance Infection of Aedes aegypti Mosquitoes. McGee, Charles E.; Tsetsarkin, Konstantin; Vanlandingham, Dana L.; McElroy, Kate L.; Lang, Jean; Guy, Bruno; Decelle, Thierry; Higgs, Stephen // Journal of Infectious Diseases;3/1/2008, Vol. 197 Issue 5, p686 

    To address concerns that a flavivirus vaccine/wild-type recombinant virus might have a high mosquito infectivity phenotype, the yellow fever virus (YFV) 17D backbone of the ChimeriVax-dengue 4 virus was replaced with the corresponding gene sequences of the virulent YFV Asibi strain....

  • Independent Nurse: Yellow Fever - New antibody hope.  // GP: General Practitioner;10/7/2005, p104 

    This article reports that the U.S. researchers have discovered an antibody that binds to viruses, such as yellow fever, West Nile virus and dengue fever, after they have attached themselves to cell surfaces. Vaccines currently block virus attachment to a cell but the new antibody can block virus...

  • Diagnosis and management of dengue. Teixeira, Maria glória; Barreto, Mauricio L. // BMJ: British Medical Journal (Overseas & Retired Doctors Edition;11/21/2009, Vol. 339 Issue 7731, p1189 

    The article offers information on the diagnosis and management of dengue. The reduction of deaths from endemic countries through organized healthcare systems is discussed. The four serotypes of the dengue virus, which is a single stranded RNA virus of the Flaviridae family, are the DENV-1,...

  • NF90 Binds the Dengue Virus RNA 3' Terminus and Is a Positive Regulator of Dengue Virus Replication. Gomila, Raúl C.; Martin,III., Glover W.; Gehrke, Lee // PLoS ONE;2011, Vol. 6 Issue 2, p1 

    Background: Viral RNA translation and replication are regulated by sequence and structural elements in the 5' and 3' untranslated regions (UTR) and by host cell and/or viral proteins that bind them. Dengue virus has a single-stranded RNA genome with positive polarity, a 5' m7GpppG cap, and a...

  • Dengue virus infection alters post-transcriptional modification of microRNAs in the mosquito vector Aedes aegypti. Etebari, Kayvan; Osei-Amo, Solomon; Blomberg, Simon Phillip; Asgari, Sassan // Scientific Reports;10/30/2015, p15968 

    Recent discoveries regarding the importance of isomiRs have increased our understanding of the regulatory complexities of the miRNAome. Observed changes in the miRNA profiles in mosquitoes infected with flaviviruses have implicated small RNAs in the interactions between viruses and their...

  • Relationship of Preexisting Dengue Virus (DV) Neutralizing Antibody Levels to Viremia and Severity of Disease in a Prospective Cohort Study of DV Infection in Thailand. Endy, Timothy P.; Nisalak, Ananda; Chunsuttitwat, Supamit; Vaughn, David W.; Green, Sharone; Ennis, Francis A.; Rothman, Alan L.; Libraty, Daniel H. // Journal of Infectious Diseases;3/15/2004, Vol. 189 Issue 6, p990 

    Background. Infection with any 1 of the 4 dengue viruses (DVs) can produce several illnesses, ranging from a mild febrile illness to classic dengue fever (DF) to dengue hemorrhagic fever (DHF), a potentially life-threatening disease. Most DHF cases occur after sequential heterotypic DV...

  • Diversity and Origin of Dengue Virus Serotypes 1, 2, and 3, Bhutan. Dorji, Tandin; In-Kyu Yoon; Holmes, Edward C.; Wangchuk, Sonam; Tobgay, Tashi; Ananda Nisalak; Piyawan Chinnawirotpisan; Kanittha Sangkachantaranon; Gibbons, Robert V.; Jarman, Richard G. // Emerging Infectious Diseases;Oct2009, Vol. 15 Issue 10, p1630 

    To determine the serotype and genotype of dengue virus (DENV) in Bhutan, we conducted phylogenetic analyses of complete envelope gene sequences. DENV-2 (Cosmopolitan genotype) predominated in 2004, and DENV-3 (genotype III) predominated in 2005-2006; these viruses were imported from India....

  • The Human Dengue Challenge Experience at the Walter Reed Army Institute of Research. Lyons, Arthur G. // Journal of Infectious Diseases;Jun2014, Vol. 209 Issue suppl_2, pS49 

    Recent discordance between measured levels of serotypes of dengue virus neutralizing antibody and clinical outcomes suggests a need to reevaluate the process of prescreening dengue vaccine candidates to better predict their clinical benefit before initiation of large-scale human vaccine trials....

  • A Promising, Single-Dose, Live Attenuated Tetravalent Dengue Vaccine Candidate. McArthur, Monica A.; Edelman, Robert // Journal of Infectious Diseases;9/1/2015, Vol. 212 Issue 5, p681 

    The authors offer information on a study related to live attenuated tetravalent dengue vaccine (LATV), a potentially important advance in dengue vaccine that is administered as a single subcutaneous injection published within the issue is presented. It also discusses expanding global health...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics