Novel chikungunya vaccine candidate with an ires-based attenuation and host range alteration mechanism

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 Weaver

Research output: Contribution to journalArticle

101 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere1002142
JournalPLoS Pathogens
Volume7
Issue number7
DOIs
StatePublished - Jul 2011

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Host Specificity
Culicidae
Vaccines
Chikungunya virus
Encephalomyocarditis virus
Alphavirus
Disease Vectors
Arthralgia
Virus Diseases
Interferons
Immunity
Complementary DNA
Clone Cells
Technology
Gene Expression
Costs and Cost Analysis
Infection
Population
Proteins
Internal Ribosome Entry Sites

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

Cite this

Novel chikungunya vaccine candidate with an ires-based attenuation and host range alteration mechanism. / Plante, Kenneth; Wang, Eryu; Partidos, Charalambos D.; Weger, James; Gorchakov, Rodion; Tsetsarkin, Konstantin; Borland, Erin M.; Powers, Ann M.; Seymour, Robert; Stinchcomb, Dan T.; Osorio, Jorge E.; Frolov, Ilya; Weaver, Scott.

In: PLoS Pathogens, Vol. 7, No. 7, e1002142, 07.2011.

Research output: Contribution to journalArticle

Plante, K, Wang, E, Partidos, CD, Weger, J, Gorchakov, R, Tsetsarkin, K, Borland, EM, Powers, AM, Seymour, R, Stinchcomb, DT, Osorio, JE, Frolov, I & Weaver, S 2011, 'Novel chikungunya vaccine candidate with an ires-based attenuation and host range alteration mechanism', PLoS Pathogens, vol. 7, no. 7, e1002142. https://doi.org/10.1371/journal.ppat.1002142
Plante, Kenneth ; Wang, Eryu ; Partidos, Charalambos D. ; Weger, James ; Gorchakov, Rodion ; Tsetsarkin, Konstantin ; Borland, Erin M. ; Powers, Ann M. ; Seymour, Robert ; Stinchcomb, Dan T. ; Osorio, Jorge E. ; Frolov, Ilya ; Weaver, Scott. / Novel chikungunya vaccine candidate with an ires-based attenuation and host range alteration mechanism. In: PLoS Pathogens. 2011 ; Vol. 7, No. 7.
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