Limited replication of yellow fever 17DD and 17D-Dengue recombinant viruses in rhesus monkeys

For the development of safe live attenuated flavivirus vaccines one of the main properties to be established is viral replication. We have used real-time reverse transcriptase-polymerase chain reaction and virus titration by plaque assay to determine the replication of yellow fever 17DD virus (YFV 1...

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Published in:	Anais da Academia Brasileira de Ciências Vol. 80; no. 2; pp. 311 - 321
Main Authors:	Trindade, Gisela F, Marchevsky, Renato S, Fillipis, Ana M B de, Nogueira, Rita M R, Bonaldo, Myrna C, Acero, Pedro C, Caride, Elena, Freire, Marcos S, Galler, Ricardo
Format:	Journal Article
Language:	English
Published:	Brazil Academia Brasileira de Ciências 01-06-2008
Subjects:	Animals Antibodies, Viral atenuação attenuation dengue Dengue Vaccines - immunology Dengue virus Dengue Virus - immunology Dengue Virus - physiology febre amarela Flavivirus Macaca mulatta MULTIDISCIPLINARY SCIENCES real-time RT-PCR Recombination, Genetic - immunology replication replicação Reverse Transcriptase Polymerase Chain Reaction RNA, Viral - blood RNA, Viral - immunology RT-PCR em tempo integral vaccine Vaccines, Attenuated - immunology vacina Viral Load Viremia - immunology Virus Replication yellow fever Yellow Fever Vaccine - immunology Yellow fever virus - immunology Yellow fever virus - physiology replication vaccine RT-PCR em tempo integral attenuation replicação yellow fever vacina febre amarela atenuação real-time RT-PCR dengue
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Summary:	For the development of safe live attenuated flavivirus vaccines one of the main properties to be established is viral replication. We have used real-time reverse transcriptase-polymerase chain reaction and virus titration by plaque assay to determine the replication of yellow fever 17DD virus (YFV 17DD) and recombinant yellow fever 17D viruses expressing envelope proteins of dengue virus serotypes 2 and 4 (17D-DENV-2 and 17D-DENV-4). Serum samples from rhesus monkeys inoculated with YFV 17DD and 17D-DENV chimeras by intracerebral or subcutaneous route were used to determine and compare the viremia induced by these viruses. Viral load quantification in samples from monkeys inoculated by either route with YFV 17DD virus suggested a restricted capability of the virus to replicate reaching not more than 2.0 log10 PFU mL(-1) or 3.29 log10 copies mL(-1). Recombinant 17D-dengue viruses were shown by plaquing and real-time PCR to be as attenuated as YF 17DD virus with the highest mean peak titer of 1.97 log10 PFU mL(-1) or 3.53 log10 copies mL(-1). These data serve as a comparative basis for the characterization of other 17D-based live attenuated candidate vaccines against other diseases.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0001-3765 1678-2690 0001-3765 1678-2690
DOI:	10.1590/S0001-37652008000200009