A cDNA Clone-Launched platform for high-yield production of inactivated Zika vaccine
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Digital do Instituto Evandro Chagas (Patuá) |
Texto Completo: | https://patua.iec.gov.br/handle/iec/2756 |
Resumo: | A purified inactivated vaccine (PIV) using the Zika virus (ZIKV) Puerto Rico strain PRVABC59 showed efficacy in monkeys, and is currently in a phase I clinical trial. High-yield manufacture of this PIV is essential for its development and vaccine access. Here we report an infectious cDNA clone-launched platform to maximize its yield. A single NS1 protein substitution (K265E) was identified to increase ZIKV replication on Vero cells (a cell line approved for vaccine production) for both Cambodian FSS13025 and Puerto Rico PRVABC59 strains. The NS1 mutation did not affect viral RNA synthesis, but significantly increased virion assembly through an increased interaction between NS1 and NS2A (a known regulator of flavivirus assembly). The NS1 mutant virus retained wild-type virulence in the A129 mouse model, but decreased its competence to infect Aedes aegypti mosquitoes. To further increase virus yield, we constructed an infectious cDNA clone of the clinical trial PIV strain PRVABC59 containing three viral replication-enhancing mutations (NS1 K265E, prM H83R, and NS3 S356F). The mutant cDNA clone produced >25-fold more ZIKV than the wild-type parent on Vero cells. This cDNA clone-launched manufacture platform has the advantages of higher virus yield, shortened manufacture time, and minimized chance of contamination. |
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Yang, YujiaoShan, ChaoZou, JingMuruato, Antonio ENunes, Bruno Tardelli DinizMedeiros, Daniele Barbosa de AlmeidaVasconcelos, Pedro Fernando da CostaRossi, Shannan LWeaver, Scott CXie, XupingShi, Pei-Yong2017-09-21T13:58:45Z2017-09-21T13:58:45Z2017YANG, Yujiao et al. A cDNA Clone-Launched platform for high-yield production of inactivated Zika vaccine. EBioMedicine, v. 17, p. 145–156, Mar. 2017.2352-3964https://patua.iec.gov.br/handle/iec/275610.1016/j.ebiom.2017.02.003A purified inactivated vaccine (PIV) using the Zika virus (ZIKV) Puerto Rico strain PRVABC59 showed efficacy in monkeys, and is currently in a phase I clinical trial. High-yield manufacture of this PIV is essential for its development and vaccine access. Here we report an infectious cDNA clone-launched platform to maximize its yield. A single NS1 protein substitution (K265E) was identified to increase ZIKV replication on Vero cells (a cell line approved for vaccine production) for both Cambodian FSS13025 and Puerto Rico PRVABC59 strains. The NS1 mutation did not affect viral RNA synthesis, but significantly increased virion assembly through an increased interaction between NS1 and NS2A (a known regulator of flavivirus assembly). The NS1 mutant virus retained wild-type virulence in the A129 mouse model, but decreased its competence to infect Aedes aegypti mosquitoes. To further increase virus yield, we constructed an infectious cDNA clone of the clinical trial PIV strain PRVABC59 containing three viral replication-enhancing mutations (NS1 K265E, prM H83R, and NS3 S356F). The mutant cDNA clone produced >25-fold more ZIKV than the wild-type parent on Vero cells. This cDNA clone-launched manufacture platform has the advantages of higher virus yield, shortened manufacture time, and minimized chance of contamination.P.Y.S. was supported by University of Texas Medical Branch (UTMB) startup award, UTMB Innovation and Commercialization award, University of Texas STARs Award, NIH grant R01AI087856, Pan American Health Organization grant SCON2016-01353, and UTMB CTSA UL1TR- 001439. This research was also supported by NIH grant AI120942 to S.C.WUniversity of Texas Medical Branch. Department of Biochemistry & Molecular Biology. Galveston, TX, USA / University, Chongqing. College of Animal Science and Technology. Southwest, China.University of Texas Medical Branch. Department of Biochemistry & Molecular Biology. Galveston, TX, USA.University of Texas Medical Branch. Department of Biochemistry & Molecular Biology. Galveston, TX, USA.Institute for Human Infections & Immunity. Galveston, TX, USA / Institute for Translational Science. Galveston, TX, USA.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil / University of Texas Medical Branch. Department of Biochemistry & Molecular Biology. Galveston, TX, USA.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil / University of Texas Medical Branch. Department of Biochemistry & Molecular Biology. Galveston, TX, USA.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil / Pará State University. Department of Pathology. Belém, PA, Brazil.Institute for Human Infections & Immunity. Galveston, TX, USA / Center for Biodefense & Emerging Infectious Diseases. Department of Pathology. Galveston, TX, USA.Institute for Human Infections & Immunity. Galveston, TX, USA / Institute for Translational Science. Galveston, TX, USA / Department of Microbiology & Immunology. Galveston, TX, USA / Sealy Center for Vaccine Development. Galveston, TX, USA / University of Texas Medical Branch. Sealy Center for Structural Biology & Molecular Biophysics. Galveston, TX, USA.University of Texas Medical Branch. Department of Biochemistry & Molecular Biology. Galveston, TX, USA.University of Texas Medical Branch. Department of Biochemistry & Molecular Biology. Galveston, TX, USA / Institute for Translational Science. Galveston, TX, USA / University of Texas Medical Branch. Sealy Center for Structural Biology & Molecular Biophysics. Galveston, TX, USA / Pará State University. Department of Pathology. Belém, PA, Brazil / University of Texas Medical Branch. Department of Pharmacology & Toxicology. Galveston, TX, USA.engElsevierA cDNA Clone-Launched platform for high-yield production of inactivated Zika vaccineinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleCricetinaeCricetulusZika virus / genéticaZika virus / imunologiaVacinas de DNA / genéticaVacinas de DNA / imunologiaVacinas de Produtos Inativados / genéticaVacinas de Produtos Inativados / imunologiaProteínas não Estruturais Virais / genéticaProteínas não Estruturais Virais / imunologiaDNA Complementar / genéticaAnálise Mutacional de DNACélulas VeroCélulas HEK293Imunofluorescência / métodosReação em Cadeia da Polimerase Via Transcriptase Reversa / métodosinfo:eu-repo/semantics/openAccessreponame:Repositório Digital do Instituto Evandro Chagas (Patuá)instname:Instituto Evandro Chagas (IEC)instacron:IECORIGINALA cDNA Clone-Launched platform for high-yield production of inactivated Zika vaccine.pdfA cDNA Clone-Launched platform for high-yield production of inactivated Zika vaccine.pdfapplication/pdf2301817https://patua.iec.gov.br/bitstreams/cb154718-557f-433e-b175-2a85afbdf96a/download8e071bb0dd94d144f504be687d080d7aMD51LICENSElicense.txtlicense.txttext/plain; charset=utf-871https://patua.iec.gov.br/bitstreams/c769d65c-9977-41f0-a2d1-72d69699d146/download52f1732ea66fbd1123abe39f5373b797MD52TEXTA cDNA Clone-Launched platform for high-yield production of inactivated Zika vaccine.pdf.txtA cDNA Clone-Launched platform for high-yield production of inactivated Zika vaccine.pdf.txtExtracted texttext/plain70717https://patua.iec.gov.br/bitstreams/5ee444c4-81b7-4d6b-80ee-6b4a68977cca/download084653ac2ea322ddb7db944da45aef24MD55THUMBNAILA cDNA Clone-Launched platform for high-yield production of inactivated Zika vaccine.pdf.jpgA cDNA Clone-Launched platform for high-yield production of inactivated Zika vaccine.pdf.jpgGenerated Thumbnailimage/jpeg5694https://patua.iec.gov.br/bitstreams/8aaa3a34-7f04-459d-97ed-c14515ae2206/download829545a934bfa1ed5530102849ac5ee0MD56iec/27562022-11-07 17:57:06.386oai:patua.iec.gov.br:iec/2756https://patua.iec.gov.brRepositório InstitucionalPUBhttps://patua.iec.gov.br/oai/requestclariceneta@iec.gov.br || Biblioteca@iec.gov.bropendoar:2022-11-07T17:57:06Repositório Digital do Instituto Evandro Chagas (Patuá) - Instituto Evandro Chagas (IEC)falseVG9kb3Mgb3MgZG9jdW1lbnRvcyBkZXNzYSBjb2xlw6fDo28gc2VndWVtIGEgTGljZW7Dp2EgQ3JlYXRpdmUgY29tbW9ucy4= |
dc.title.pt_BR.fl_str_mv |
A cDNA Clone-Launched platform for high-yield production of inactivated Zika vaccine |
title |
A cDNA Clone-Launched platform for high-yield production of inactivated Zika vaccine |
spellingShingle |
A cDNA Clone-Launched platform for high-yield production of inactivated Zika vaccine Yang, Yujiao Cricetinae Cricetulus Zika virus / genética Zika virus / imunologia Vacinas de DNA / genética Vacinas de DNA / imunologia Vacinas de Produtos Inativados / genética Vacinas de Produtos Inativados / imunologia Proteínas não Estruturais Virais / genética Proteínas não Estruturais Virais / imunologia DNA Complementar / genética Análise Mutacional de DNA Células Vero Células HEK293 Imunofluorescência / métodos Reação em Cadeia da Polimerase Via Transcriptase Reversa / métodos |
title_short |
A cDNA Clone-Launched platform for high-yield production of inactivated Zika vaccine |
title_full |
A cDNA Clone-Launched platform for high-yield production of inactivated Zika vaccine |
title_fullStr |
A cDNA Clone-Launched platform for high-yield production of inactivated Zika vaccine |
title_full_unstemmed |
A cDNA Clone-Launched platform for high-yield production of inactivated Zika vaccine |
title_sort |
A cDNA Clone-Launched platform for high-yield production of inactivated Zika vaccine |
author |
Yang, Yujiao |
author_facet |
Yang, Yujiao Shan, Chao Zou, Jing Muruato, Antonio E Nunes, Bruno Tardelli Diniz Medeiros, Daniele Barbosa de Almeida Vasconcelos, Pedro Fernando da Costa Rossi, Shannan L Weaver, Scott C Xie, Xuping Shi, Pei-Yong |
author_role |
author |
author2 |
Shan, Chao Zou, Jing Muruato, Antonio E Nunes, Bruno Tardelli Diniz Medeiros, Daniele Barbosa de Almeida Vasconcelos, Pedro Fernando da Costa Rossi, Shannan L Weaver, Scott C Xie, Xuping Shi, Pei-Yong |
author2_role |
author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Yang, Yujiao Shan, Chao Zou, Jing Muruato, Antonio E Nunes, Bruno Tardelli Diniz Medeiros, Daniele Barbosa de Almeida Vasconcelos, Pedro Fernando da Costa Rossi, Shannan L Weaver, Scott C Xie, Xuping Shi, Pei-Yong |
dc.subject.decsPrimary.pt_BR.fl_str_mv |
Cricetinae Cricetulus Zika virus / genética Zika virus / imunologia Vacinas de DNA / genética Vacinas de DNA / imunologia Vacinas de Produtos Inativados / genética Vacinas de Produtos Inativados / imunologia Proteínas não Estruturais Virais / genética Proteínas não Estruturais Virais / imunologia DNA Complementar / genética Análise Mutacional de DNA Células Vero Células HEK293 Imunofluorescência / métodos Reação em Cadeia da Polimerase Via Transcriptase Reversa / métodos |
topic |
Cricetinae Cricetulus Zika virus / genética Zika virus / imunologia Vacinas de DNA / genética Vacinas de DNA / imunologia Vacinas de Produtos Inativados / genética Vacinas de Produtos Inativados / imunologia Proteínas não Estruturais Virais / genética Proteínas não Estruturais Virais / imunologia DNA Complementar / genética Análise Mutacional de DNA Células Vero Células HEK293 Imunofluorescência / métodos Reação em Cadeia da Polimerase Via Transcriptase Reversa / métodos |
description |
A purified inactivated vaccine (PIV) using the Zika virus (ZIKV) Puerto Rico strain PRVABC59 showed efficacy in monkeys, and is currently in a phase I clinical trial. High-yield manufacture of this PIV is essential for its development and vaccine access. Here we report an infectious cDNA clone-launched platform to maximize its yield. A single NS1 protein substitution (K265E) was identified to increase ZIKV replication on Vero cells (a cell line approved for vaccine production) for both Cambodian FSS13025 and Puerto Rico PRVABC59 strains. The NS1 mutation did not affect viral RNA synthesis, but significantly increased virion assembly through an increased interaction between NS1 and NS2A (a known regulator of flavivirus assembly). The NS1 mutant virus retained wild-type virulence in the A129 mouse model, but decreased its competence to infect Aedes aegypti mosquitoes. To further increase virus yield, we constructed an infectious cDNA clone of the clinical trial PIV strain PRVABC59 containing three viral replication-enhancing mutations (NS1 K265E, prM H83R, and NS3 S356F). The mutant cDNA clone produced >25-fold more ZIKV than the wild-type parent on Vero cells. This cDNA clone-launched manufacture platform has the advantages of higher virus yield, shortened manufacture time, and minimized chance of contamination. |
publishDate |
2017 |
dc.date.accessioned.fl_str_mv |
2017-09-21T13:58:45Z |
dc.date.available.fl_str_mv |
2017-09-21T13:58:45Z |
dc.date.issued.fl_str_mv |
2017 |
dc.type.status.fl_str_mv |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
dc.identifier.citation.fl_str_mv |
YANG, Yujiao et al. A cDNA Clone-Launched platform for high-yield production of inactivated Zika vaccine. EBioMedicine, v. 17, p. 145–156, Mar. 2017. |
dc.identifier.uri.fl_str_mv |
https://patua.iec.gov.br/handle/iec/2756 |
dc.identifier.issn.-.fl_str_mv |
2352-3964 |
dc.identifier.doi.-.fl_str_mv |
10.1016/j.ebiom.2017.02.003 |
identifier_str_mv |
YANG, Yujiao et al. A cDNA Clone-Launched platform for high-yield production of inactivated Zika vaccine. EBioMedicine, v. 17, p. 145–156, Mar. 2017. 2352-3964 10.1016/j.ebiom.2017.02.003 |
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Elsevier |
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Elsevier |
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