Chikungunya virus vaccine candidates with decreased mutational robustness are attenuated in vivo and have compromised transmissibility
Chikungunya virus (CHIKV) is a reemerged arbovirus, a member of the Togaviridae family. It circulates through mosquito vectors mainly of the Aedes family and a mammalian host. CHIKV causes chikungunya fever, a mild to severe disease characterized by arthralgia, with some fatal outcomes described. In...
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| Ētahi atu kaituhi: | , , , , , , , , |
| Hōputu: | article |
| Reo: | Ingarihi |
| I whakaputaina: |
2019
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| Ngā marau: | |
| Urunga tuihono: | https://hdl.handle.net/20.500.12008/27807 |
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Kāore He Tūtohu, Me noho koe te mea tuatahi ki te tūtohu i tēnei pūkete!
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| _version_ | 1868890072406818816 |
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| author | Carrau Eguía, Lucía |
| author2 | Rezelj, V. Noval, M. Levi, L. Megrian, Daniela Blanc, H. Weger-Lucarelli, J. Moratorio, Gonzalo Stapleford, K. Vignuzzi, Marco |
| author2_role | author author author author author author author author author |
| author_browse | Blanc, H. Carrau Eguía, Lucía Levi, L. Megrian, Daniela Moratorio, Gonzalo Noval, M. Rezelj, V. Stapleford, K. Vignuzzi, Marco Weger-Lucarelli, J. |
| author_facet | Carrau Eguía, Lucía Rezelj, V. Noval, M. Levi, L. Megrian, Daniela Blanc, H. Weger-Lucarelli, J. Moratorio, Gonzalo Stapleford, K. Vignuzzi, Marco |
| author_role | author |
| collection | COLIBRI |
| dc.contributor.none.fl_str_mv | Carrau Eguía Lucía, Instituo Pasteur (Francia) Rezelj V. Noval M. Levi L. Megrian D., Instituo Pasteur (Francia) Blanc H. Weger-Lucarelli J. Moratorio Gonzalo, Universidad de la República (Uruguay). Facultad de Ciencias. Centro de Investigaciones Nucleares. Stapleford K. Vignuzzi Marco, Instituo Pasteur (Francia) |
| dc.creator.none.fl_str_mv | Carrau Eguía, Lucía Rezelj, V. Noval, M. Levi, L. Megrian, Daniela Blanc, H. Weger-Lucarelli, J. Moratorio, Gonzalo Stapleford, K. Vignuzzi, Marco |
| dc.date.none.fl_str_mv | 2019 2021-05-24T13:21:48Z 2021-05-24T13:21:48Z |
| dc.format.none.fl_str_mv | 20 h. application/pdf |
| dc.identifier.none.fl_str_mv | Carrau Eguía, L, Rezelj, V, Noval, M, y otros "Chikungunya virus vaccine candidates with decreased mutational robustness are attenuated in vivo and have compromised transmissibility". Journal of Virology. [en línea] 2019, 93(18): e00775-19. 20 h. DOI: 10.1128/JVI.00775-19 1098-5514 https://hdl.handle.net/20.500.12008/27807 10.1128/JVI.00775-19 |
| dc.language.none.fl_str_mv | en eng |
| dc.publisher.none.fl_str_mv | American Society for Microbiology |
| dc.relation.none.fl_str_mv | Journal of Virology, 2019, 93(18): e00775-19 |
| dc.rights.none.fl_str_mv | info:eu-repo/semantics/openAccess Licencia Creative Commons Atribución (CC - By 4.0) |
| dc.source.none.fl_str_mv | reponame:COLIBRI instname:Universidad de la República instacron:Universidad de la República |
| dc.subject.none.fl_str_mv | Chikungunya Mutational robustness Vaccines |
| dc.title.none.fl_str_mv | Chikungunya virus vaccine candidates with decreased mutational robustness are attenuated in vivo and have compromised transmissibility |
| dc.type.none.fl_str_mv | Artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
| description | Chikungunya virus (CHIKV) is a reemerged arbovirus, a member of the Togaviridae family. It circulates through mosquito vectors mainly of the Aedes family and a mammalian host. CHIKV causes chikungunya fever, a mild to severe disease characterized by arthralgia, with some fatal outcomes described. In the past years, several outbreaks mainly caused by enhanced adaptation of the virus to the vector and ineffective control of the contacts between infected mosquito populations and the human host have been reported. Vaccines represent the best solution for the control of insect-borne viruses, including CHIKV, but are often unavailable. We designed live attenuated CHIKVs by applying a rational genomic design based on multiple replacements of synonymous codons. In doing so, the virus mutational robustness (capacity to maintain phenotype despite introduction of mutations to genotype) is decreased, driving the viral population toward deleterious evolutionary trajectories. When the candidate viruses were tested in the insect and mammalian hosts, we observed overall strong attenuation in both and greatly diminished signs of disease. Moreover, we found that the vaccine candidates elicited protective immunity related to the production of neutralizing antibodies after a single dose. During an experimental transmission cycle between mosquitoes and naive mice, vaccine candidates could be transmitted by mosquito bite, leading to asymptomatic infection in mice with compromised dissemination. Using deep-sequencing technology, we observed an increase in detrimental (stop) codons, which confirmed the effectiveness of this genomic design. Because the approach involves hundreds of synonymous modifications to the genome, the reversion risk is significantly reduced, rendering the viruses promising vaccine candidates. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | anni_5cbb21937fb32dfcfd609e86d07add0e |
| identifier_str_mv | Carrau Eguía, L, Rezelj, V, Noval, M, y otros "Chikungunya virus vaccine candidates with decreased mutational robustness are attenuated in vivo and have compromised transmissibility". Journal of Virology. [en línea] 2019, 93(18): e00775-19. 20 h. DOI: 10.1128/JVI.00775-19 1098-5514 10.1128/JVI.00775-19 |
| instacron_str | Universidad de la República |
| institution | Universidad de la República |
| instname_str | Universidad de la República |
| language | eng |
| language_invalid_str_mv | en |
| network_acronym_str | anni |
| network_name_str | oai-lr-anni |
| oai_identifier_str | oai:colibri.udelar.edu.uy:20.500.12008/27807 |
| publishDate | 2019 |
| publishDateSort | 2019 |
| publisher.none.fl_str_mv | American Society for Microbiology |
| reponame_str | COLIBRI |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | Licencia Creative Commons Atribución (CC - By 4.0) |
| spelling | Chikungunya virus vaccine candidates with decreased mutational robustness are attenuated in vivo and have compromised transmissibilityCarrau Eguía, LucíaRezelj, V.Noval, M.Levi, L.Megrian, DanielaBlanc, H.Weger-Lucarelli, J.Moratorio, GonzaloStapleford, K.Vignuzzi, MarcoChikungunyaMutational robustnessVaccinesChikungunya virus (CHIKV) is a reemerged arbovirus, a member of the Togaviridae family. It circulates through mosquito vectors mainly of the Aedes family and a mammalian host. CHIKV causes chikungunya fever, a mild to severe disease characterized by arthralgia, with some fatal outcomes described. In the past years, several outbreaks mainly caused by enhanced adaptation of the virus to the vector and ineffective control of the contacts between infected mosquito populations and the human host have been reported. Vaccines represent the best solution for the control of insect-borne viruses, including CHIKV, but are often unavailable. We designed live attenuated CHIKVs by applying a rational genomic design based on multiple replacements of synonymous codons. In doing so, the virus mutational robustness (capacity to maintain phenotype despite introduction of mutations to genotype) is decreased, driving the viral population toward deleterious evolutionary trajectories. When the candidate viruses were tested in the insect and mammalian hosts, we observed overall strong attenuation in both and greatly diminished signs of disease. Moreover, we found that the vaccine candidates elicited protective immunity related to the production of neutralizing antibodies after a single dose. During an experimental transmission cycle between mosquitoes and naive mice, vaccine candidates could be transmitted by mosquito bite, leading to asymptomatic infection in mice with compromised dissemination. Using deep-sequencing technology, we observed an increase in detrimental (stop) codons, which confirmed the effectiveness of this genomic design. Because the approach involves hundreds of synonymous modifications to the genome, the reversion risk is significantly reduced, rendering the viruses promising vaccine candidates.American Society for MicrobiologyCarrau Eguía Lucía, Instituo Pasteur (Francia)Rezelj V.Noval M.Levi L.Megrian D., Instituo Pasteur (Francia)Blanc H.Weger-Lucarelli J.Moratorio Gonzalo, Universidad de la República (Uruguay). Facultad de Ciencias. Centro de Investigaciones Nucleares.Stapleford K.Vignuzzi Marco, Instituo Pasteur (Francia)2021-05-24T13:21:48Z2021-05-24T13:21:48Z2019Artículoinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion20 h.application/pdfCarrau Eguía, L, Rezelj, V, Noval, M, y otros "Chikungunya virus vaccine candidates with decreased mutational robustness are attenuated in vivo and have compromised transmissibility". Journal of Virology. [en línea] 2019, 93(18): e00775-19. 20 h. DOI: 10.1128/JVI.00775-191098-5514https://hdl.handle.net/20.500.12008/2780710.1128/JVI.00775-19reponame:COLIBRIinstname:Universidad de la Repúblicainstacron:Universidad de la RepúblicaenengJournal of Virology, 2019, 93(18): e00775-19Las obras depositadas en el Repositorio se rigen por la Ordenanza de los Derechos de la Propiedad Intelectual de la Universidad de la República.(Res. Nº 91 de C.D.C. de 8/III/1994 – D.O. 7/IV/1994) y por la Ordenanza del Repositorio Abierto de la Universidad de la República (Res. Nº 16 de C.D.C. de 07/10/2014)info:eu-repo/semantics/openAccessLicencia Creative Commons Atribución (CC - By 4.0)oai:colibri.udelar.edu.uy:20.500.12008/278072026-04-14T10:09:37Z |
| spellingShingle | Chikungunya virus vaccine candidates with decreased mutational robustness are attenuated in vivo and have compromised transmissibility Carrau Eguía, Lucía Chikungunya Mutational robustness Vaccines |
| status_str | publishedVersion |
| title | Chikungunya virus vaccine candidates with decreased mutational robustness are attenuated in vivo and have compromised transmissibility |
| title_full | Chikungunya virus vaccine candidates with decreased mutational robustness are attenuated in vivo and have compromised transmissibility |
| title_fullStr | Chikungunya virus vaccine candidates with decreased mutational robustness are attenuated in vivo and have compromised transmissibility |
| title_full_unstemmed | Chikungunya virus vaccine candidates with decreased mutational robustness are attenuated in vivo and have compromised transmissibility |
| title_short | Chikungunya virus vaccine candidates with decreased mutational robustness are attenuated in vivo and have compromised transmissibility |
| title_sort | Chikungunya virus vaccine candidates with decreased mutational robustness are attenuated in vivo and have compromised transmissibility |
| topic | Chikungunya Mutational robustness Vaccines |
| url | https://hdl.handle.net/20.500.12008/27807 |