title: Novel chikungunya vaccine candidate with an IRES-based attenuation and host range alteration mechanism.
abstract: 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.
authors.affiliation: Institute for Human Infections and Immunity, Sealy Center for Vaccine Development, and Department of Pathology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Plante
authors.forename: Eryu
authors.initials: E
authors.lastname: Wang
authors.forename: Charalambos D
authors.initials: CD
authors.lastname: Partidos
authors.forename: James
authors.initials: J
authors.lastname: Weger
authors.forename: Rodion
authors.initials: R
authors.lastname: Gorchakov
authors.forename: Konstantin
authors.initials: K
authors.lastname: Tsetsarkin
authors.forename: Erin M
authors.initials: EM
authors.lastname: Borland
authors.forename: Ann M
authors.initials: AM
authors.lastname: Powers
authors.forename: Robert
authors.initials: R
authors.lastname: Seymour
authors.forename: Dan T
authors.initials: DT
authors.lastname: Stinchcomb
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Osorio
authors.forename: Ilya
authors.initials: I
authors.lastname: Frolov
authors.forename: Scott C
authors.initials: SC
authors.lastname: Weaver
mesh_terms: D018354:Alphavirus Infections / Q000235:genetics / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D000818:Animals; D001179:Arthropod Vectors / Q000276:immunology / Q000821:virology; D065632:Chikungunya Fever; D002646:Chikungunya virus / Q000235:genetics / Q000276:immunology; D002522:Chlorocebus aethiops; D058507:Host Specificity / Q000235:genetics / Q000276:immunology*; D051379:Mice; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology; D014709:Vero Cells; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology
chemical_list: D014613:Vaccines, Attenuated; D014765:Viral Vaccines