Attenuation and immunogenicity of recombinant yellow fever 17D-dengue type 2 virus for rhesus monkeys
A chimeric yellow fever (YF)-dengue serotype 2 (dengue 2) virus was constructed by replacing the premembrane and envelope genes of the YF 17D virus with those from dengue 2 virus strains of Southeast Asian genotype. The virus grew to high titers in Vero cells and, after passage 2, was used for immunogenicity and attenuation studies in rhesus monkeys. Subcutaneous immunization of naive rhesus monkeys with the 17D-D2 chimeric virus induced a neutralizing antibody response associated with the protection of 6 of 7 monkeys against viremia by wild-type dengue 2 virus. Neutralizing antibody titers to dengue 2 were significantly lower in YF-immune animals than in YF-naive monkeys and protection against challenge with wild-type dengue 2 virus was observed in only 2 of 11 YF-immune monkeys. An anamnestic response to dengue 2, indicated by a sharp increase of neutralizing antibody titers, was observed in the majority of the monkeys after challenge with wild-type virus. Virus attenuation was demonstrated using the standard monkey neurovirulence test. The 17D-D2 chimera caused significantly fewer histological lesions than the YF 17DD virus. The attenuated phenotype could also be inferred from the limited viremias compared to the YF 17DD vaccine. Overall, these results provide further support for the use of chimeric viruses for the development of a new live tetravalent dengue vaccine.
Main Authors: | , , , , , , , , , |
---|---|
Format: | Digital revista |
Language: | English |
Published: |
Associação Brasileira de Divulgação Científica
2005
|
Online Access: | http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2005001200012 |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
id |
oai:scielo:S0100-879X2005001200012 |
---|---|
record_format |
ojs |
spelling |
oai:scielo:S0100-879X20050012000122005-11-09Attenuation and immunogenicity of recombinant yellow fever 17D-dengue type 2 virus for rhesus monkeysGaller,R.Marchevsky,R.S.Caride,E.Almeida,L.F.C.Yamamura,A.M.Y.Jabor,A.V.Motta,M.C.A.Bonaldo,M.C.Coutinho,E.S.F.Freire,M.S. YF 17D virus recombinants Dengue vaccine Immunogenicity Attenuation Rhesus monkeys A chimeric yellow fever (YF)-dengue serotype 2 (dengue 2) virus was constructed by replacing the premembrane and envelope genes of the YF 17D virus with those from dengue 2 virus strains of Southeast Asian genotype. The virus grew to high titers in Vero cells and, after passage 2, was used for immunogenicity and attenuation studies in rhesus monkeys. Subcutaneous immunization of naive rhesus monkeys with the 17D-D2 chimeric virus induced a neutralizing antibody response associated with the protection of 6 of 7 monkeys against viremia by wild-type dengue 2 virus. Neutralizing antibody titers to dengue 2 were significantly lower in YF-immune animals than in YF-naive monkeys and protection against challenge with wild-type dengue 2 virus was observed in only 2 of 11 YF-immune monkeys. An anamnestic response to dengue 2, indicated by a sharp increase of neutralizing antibody titers, was observed in the majority of the monkeys after challenge with wild-type virus. Virus attenuation was demonstrated using the standard monkey neurovirulence test. The 17D-D2 chimera caused significantly fewer histological lesions than the YF 17DD virus. The attenuated phenotype could also be inferred from the limited viremias compared to the YF 17DD vaccine. Overall, these results provide further support for the use of chimeric viruses for the development of a new live tetravalent dengue vaccine.info:eu-repo/semantics/openAccessAssociação Brasileira de Divulgação CientíficaBrazilian Journal of Medical and Biological Research v.38 n.12 20052005-12-01info:eu-repo/semantics/articletext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2005001200012en10.1590/S0100-879X2005001200012 |
institution |
SCIELO |
collection |
OJS |
country |
Brasil |
countrycode |
BR |
component |
Revista |
access |
En linea |
databasecode |
rev-scielo-br |
tag |
revista |
region |
America del Sur |
libraryname |
SciELO |
language |
English |
format |
Digital |
author |
Galler,R. Marchevsky,R.S. Caride,E. Almeida,L.F.C. Yamamura,A.M.Y. Jabor,A.V. Motta,M.C.A. Bonaldo,M.C. Coutinho,E.S.F. Freire,M.S. |
spellingShingle |
Galler,R. Marchevsky,R.S. Caride,E. Almeida,L.F.C. Yamamura,A.M.Y. Jabor,A.V. Motta,M.C.A. Bonaldo,M.C. Coutinho,E.S.F. Freire,M.S. Attenuation and immunogenicity of recombinant yellow fever 17D-dengue type 2 virus for rhesus monkeys |
author_facet |
Galler,R. Marchevsky,R.S. Caride,E. Almeida,L.F.C. Yamamura,A.M.Y. Jabor,A.V. Motta,M.C.A. Bonaldo,M.C. Coutinho,E.S.F. Freire,M.S. |
author_sort |
Galler,R. |
title |
Attenuation and immunogenicity of recombinant yellow fever 17D-dengue type 2 virus for rhesus monkeys |
title_short |
Attenuation and immunogenicity of recombinant yellow fever 17D-dengue type 2 virus for rhesus monkeys |
title_full |
Attenuation and immunogenicity of recombinant yellow fever 17D-dengue type 2 virus for rhesus monkeys |
title_fullStr |
Attenuation and immunogenicity of recombinant yellow fever 17D-dengue type 2 virus for rhesus monkeys |
title_full_unstemmed |
Attenuation and immunogenicity of recombinant yellow fever 17D-dengue type 2 virus for rhesus monkeys |
title_sort |
attenuation and immunogenicity of recombinant yellow fever 17d-dengue type 2 virus for rhesus monkeys |
description |
A chimeric yellow fever (YF)-dengue serotype 2 (dengue 2) virus was constructed by replacing the premembrane and envelope genes of the YF 17D virus with those from dengue 2 virus strains of Southeast Asian genotype. The virus grew to high titers in Vero cells and, after passage 2, was used for immunogenicity and attenuation studies in rhesus monkeys. Subcutaneous immunization of naive rhesus monkeys with the 17D-D2 chimeric virus induced a neutralizing antibody response associated with the protection of 6 of 7 monkeys against viremia by wild-type dengue 2 virus. Neutralizing antibody titers to dengue 2 were significantly lower in YF-immune animals than in YF-naive monkeys and protection against challenge with wild-type dengue 2 virus was observed in only 2 of 11 YF-immune monkeys. An anamnestic response to dengue 2, indicated by a sharp increase of neutralizing antibody titers, was observed in the majority of the monkeys after challenge with wild-type virus. Virus attenuation was demonstrated using the standard monkey neurovirulence test. The 17D-D2 chimera caused significantly fewer histological lesions than the YF 17DD virus. The attenuated phenotype could also be inferred from the limited viremias compared to the YF 17DD vaccine. Overall, these results provide further support for the use of chimeric viruses for the development of a new live tetravalent dengue vaccine. |
publisher |
Associação Brasileira de Divulgação Científica |
publishDate |
2005 |
url |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2005001200012 |
work_keys_str_mv |
AT gallerr attenuationandimmunogenicityofrecombinantyellowfever17ddenguetype2virusforrhesusmonkeys AT marchevskyrs attenuationandimmunogenicityofrecombinantyellowfever17ddenguetype2virusforrhesusmonkeys AT caridee attenuationandimmunogenicityofrecombinantyellowfever17ddenguetype2virusforrhesusmonkeys AT almeidalfc attenuationandimmunogenicityofrecombinantyellowfever17ddenguetype2virusforrhesusmonkeys AT yamamuraamy attenuationandimmunogenicityofrecombinantyellowfever17ddenguetype2virusforrhesusmonkeys AT jaborav attenuationandimmunogenicityofrecombinantyellowfever17ddenguetype2virusforrhesusmonkeys AT mottamca attenuationandimmunogenicityofrecombinantyellowfever17ddenguetype2virusforrhesusmonkeys AT bonaldomc attenuationandimmunogenicityofrecombinantyellowfever17ddenguetype2virusforrhesusmonkeys AT coutinhoesf attenuationandimmunogenicityofrecombinantyellowfever17ddenguetype2virusforrhesusmonkeys AT freirems attenuationandimmunogenicityofrecombinantyellowfever17ddenguetype2virusforrhesusmonkeys |
_version_ |
1756391131005845504 |