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Vaccine candidates derived from a novel infectious cDNA clone of an American genotype dengue virus type 2

BACKGROUND: A dengue virus type 2 (DEN-2 Tonga/74) isolated from a 1974 epidemic was characterized by mild illness and belongs to the American genotype of DEN-2 viruses. To prepare a vaccine candidate, a previously described 30 nucleotide deletion (Δ30) in the 3' untranslated region of DEN-4 ha...

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Autores principales: Blaney, Joseph E, Hanson, Christopher T, Hanley, Kathryn A, Murphy, Brian R, Whitehead, Stephen S
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2004
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC524489/
https://www.ncbi.nlm.nih.gov/pubmed/15461822
http://dx.doi.org/10.1186/1471-2334-4-39
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author Blaney, Joseph E
Hanson, Christopher T
Hanley, Kathryn A
Murphy, Brian R
Whitehead, Stephen S
author_facet Blaney, Joseph E
Hanson, Christopher T
Hanley, Kathryn A
Murphy, Brian R
Whitehead, Stephen S
author_sort Blaney, Joseph E
collection PubMed
description BACKGROUND: A dengue virus type 2 (DEN-2 Tonga/74) isolated from a 1974 epidemic was characterized by mild illness and belongs to the American genotype of DEN-2 viruses. To prepare a vaccine candidate, a previously described 30 nucleotide deletion (Δ30) in the 3' untranslated region of DEN-4 has been engineered into the DEN-2 isolate. METHODS: A full-length cDNA clone was generated from the DEN-2 virus and used to produce recombinant DEN-2 (rDEN-2) and rDEN2Δ30. Viruses were evaluated for replication in SCID mice transplanted with human hepatoma cells (SCID-HuH-7 mice), in mosquitoes, and in rhesus monkeys. Neutralizing antibody induction and protective efficacy were also assessed in rhesus monkeys. RESULTS: The rDEN2Δ30 virus was ten-fold reduced in replication in SCID-HuH-7 mice when compared to the parent virus. The rDEN-2 viruses were not infectious for Aedes mosquitoes, but both readily infected Toxorynchites mosquitoes. In rhesus monkeys, rDEN2Δ30 appeared to be slightly attenuated when compared to the parent virus as measured by duration and peak of viremia and neutralizing antibody induction. A derivative of rDEN2Δ30, designated rDEN2Δ30-4995, was generated by incorporation of a point mutation previously identified in the NS3 gene of DEN-4 and was found to be more attenuated than rDEN2Δ30 in SCID-HuH-7 mice. CONCLUSIONS: The rDEN2Δ30 and rDEN2Δ30-4995 viruses can be considered for evaluation in humans and for inclusion in a tetravalent dengue vaccine.
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spelling pubmed-5244892004-10-31 Vaccine candidates derived from a novel infectious cDNA clone of an American genotype dengue virus type 2 Blaney, Joseph E Hanson, Christopher T Hanley, Kathryn A Murphy, Brian R Whitehead, Stephen S BMC Infect Dis Research Article BACKGROUND: A dengue virus type 2 (DEN-2 Tonga/74) isolated from a 1974 epidemic was characterized by mild illness and belongs to the American genotype of DEN-2 viruses. To prepare a vaccine candidate, a previously described 30 nucleotide deletion (Δ30) in the 3' untranslated region of DEN-4 has been engineered into the DEN-2 isolate. METHODS: A full-length cDNA clone was generated from the DEN-2 virus and used to produce recombinant DEN-2 (rDEN-2) and rDEN2Δ30. Viruses were evaluated for replication in SCID mice transplanted with human hepatoma cells (SCID-HuH-7 mice), in mosquitoes, and in rhesus monkeys. Neutralizing antibody induction and protective efficacy were also assessed in rhesus monkeys. RESULTS: The rDEN2Δ30 virus was ten-fold reduced in replication in SCID-HuH-7 mice when compared to the parent virus. The rDEN-2 viruses were not infectious for Aedes mosquitoes, but both readily infected Toxorynchites mosquitoes. In rhesus monkeys, rDEN2Δ30 appeared to be slightly attenuated when compared to the parent virus as measured by duration and peak of viremia and neutralizing antibody induction. A derivative of rDEN2Δ30, designated rDEN2Δ30-4995, was generated by incorporation of a point mutation previously identified in the NS3 gene of DEN-4 and was found to be more attenuated than rDEN2Δ30 in SCID-HuH-7 mice. CONCLUSIONS: The rDEN2Δ30 and rDEN2Δ30-4995 viruses can be considered for evaluation in humans and for inclusion in a tetravalent dengue vaccine. BioMed Central 2004-10-04 /pmc/articles/PMC524489/ /pubmed/15461822 http://dx.doi.org/10.1186/1471-2334-4-39 Text en Copyright © 2004 Blaney et al; licensee BioMed Central Ltd.
spellingShingle Research Article
Blaney, Joseph E
Hanson, Christopher T
Hanley, Kathryn A
Murphy, Brian R
Whitehead, Stephen S
Vaccine candidates derived from a novel infectious cDNA clone of an American genotype dengue virus type 2
title Vaccine candidates derived from a novel infectious cDNA clone of an American genotype dengue virus type 2
title_full Vaccine candidates derived from a novel infectious cDNA clone of an American genotype dengue virus type 2
title_fullStr Vaccine candidates derived from a novel infectious cDNA clone of an American genotype dengue virus type 2
title_full_unstemmed Vaccine candidates derived from a novel infectious cDNA clone of an American genotype dengue virus type 2
title_short Vaccine candidates derived from a novel infectious cDNA clone of an American genotype dengue virus type 2
title_sort vaccine candidates derived from a novel infectious cdna clone of an american genotype dengue virus type 2
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC524489/
https://www.ncbi.nlm.nih.gov/pubmed/15461822
http://dx.doi.org/10.1186/1471-2334-4-39
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