Novel chikungunya vaccine candidate with an IRES-based attenuation and host range alteration mechanism.
Chikungunya virus (CHIKV) is a reemerging mosquito-borne pathogen that has recently caused devastating urban epidemics of severe and sometimes chronic arthralgia. As with most other mosquito-borne viral diseases, control relies on reducing mosquito populations and their contact with people, which ha...
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Public Library of Science (PLoS)
2011
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oai:doaj.org-article:eac4c566b2654d0ab41db960f375abb02021-11-18T06:03:10ZNovel chikungunya vaccine candidate with an IRES-based attenuation and host range alteration mechanism.1553-73661553-737410.1371/journal.ppat.1002142https://doaj.org/article/eac4c566b2654d0ab41db960f375abb02011-07-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21829348/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Chikungunya virus (CHIKV) is a reemerging mosquito-borne pathogen that has recently caused devastating urban epidemics of severe and sometimes chronic arthralgia. As with most other mosquito-borne viral diseases, control relies on reducing mosquito populations and their contact with people, which has been ineffective in most locations. Therefore, vaccines remain the best strategy to prevent most vector-borne diseases. Ideally, vaccines for diseases of resource-limited countries should combine low cost and single dose efficacy, yet induce rapid and long-lived immunity with negligible risk of serious adverse reactions. To develop such a vaccine to protect against chikungunya fever, we employed a rational attenuation mechanism that also prevents the infection of mosquito vectors. The internal ribosome entry site (IRES) from encephalomyocarditis virus replaced the subgenomic promoter in a cDNA CHIKV clone, thus altering the levels and host-specific mechanism of structural protein gene expression. Testing in both normal outbred and interferon response-defective mice indicated that the new vaccine candidate is highly attenuated, immunogenic and efficacious after a single dose. Furthermore, it is incapable of replicating in mosquito cells or infecting mosquitoes in vivo. This IRES-based attenuation platform technology may be useful for the predictable attenuation of any alphavirus.Kenneth PlanteEryu WangCharalambos D PartidosJames WegerRodion GorchakovKonstantin TsetsarkinErin M BorlandAnn M PowersRobert SeymourDan T StinchcombJorge E OsorioIlya FrolovScott C WeaverPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 7, Iss 7, p e1002142 (2011) |
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DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 |
| spellingShingle |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Kenneth Plante Eryu Wang Charalambos D Partidos James Weger Rodion Gorchakov Konstantin Tsetsarkin Erin M Borland Ann M Powers Robert Seymour Dan T Stinchcomb Jorge E Osorio Ilya Frolov Scott C Weaver Novel chikungunya vaccine candidate with an IRES-based attenuation and host range alteration mechanism. |
| description |
Chikungunya virus (CHIKV) is a reemerging mosquito-borne pathogen that has recently caused devastating urban epidemics of severe and sometimes chronic arthralgia. As with most other mosquito-borne viral diseases, control relies on reducing mosquito populations and their contact with people, which has been ineffective in most locations. Therefore, vaccines remain the best strategy to prevent most vector-borne diseases. Ideally, vaccines for diseases of resource-limited countries should combine low cost and single dose efficacy, yet induce rapid and long-lived immunity with negligible risk of serious adverse reactions. To develop such a vaccine to protect against chikungunya fever, we employed a rational attenuation mechanism that also prevents the infection of mosquito vectors. The internal ribosome entry site (IRES) from encephalomyocarditis virus replaced the subgenomic promoter in a cDNA CHIKV clone, thus altering the levels and host-specific mechanism of structural protein gene expression. Testing in both normal outbred and interferon response-defective mice indicated that the new vaccine candidate is highly attenuated, immunogenic and efficacious after a single dose. Furthermore, it is incapable of replicating in mosquito cells or infecting mosquitoes in vivo. This IRES-based attenuation platform technology may be useful for the predictable attenuation of any alphavirus. |
| format |
article |
| author |
Kenneth Plante Eryu Wang Charalambos D Partidos James Weger Rodion Gorchakov Konstantin Tsetsarkin Erin M Borland Ann M Powers Robert Seymour Dan T Stinchcomb Jorge E Osorio Ilya Frolov Scott C Weaver |
| author_facet |
Kenneth Plante Eryu Wang Charalambos D Partidos James Weger Rodion Gorchakov Konstantin Tsetsarkin Erin M Borland Ann M Powers Robert Seymour Dan T Stinchcomb Jorge E Osorio Ilya Frolov Scott C Weaver |
| author_sort |
Kenneth Plante |
| title |
Novel chikungunya vaccine candidate with an IRES-based attenuation and host range alteration mechanism. |
| title_short |
Novel chikungunya vaccine candidate with an IRES-based attenuation and host range alteration mechanism. |
| title_full |
Novel chikungunya vaccine candidate with an IRES-based attenuation and host range alteration mechanism. |
| title_fullStr |
Novel chikungunya vaccine candidate with an IRES-based attenuation and host range alteration mechanism. |
| title_full_unstemmed |
Novel chikungunya vaccine candidate with an IRES-based attenuation and host range alteration mechanism. |
| title_sort |
novel chikungunya vaccine candidate with an ires-based attenuation and host range alteration mechanism. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2011 |
| url |
https://doaj.org/article/eac4c566b2654d0ab41db960f375abb0 |
| work_keys_str_mv |
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| _version_ |
1718424701008609280 |