IRES-driven Expression of the Capsid Protein of the Venezuelan Equine Encephalitis Virus TC-83 Vaccine Strain Increases Its Attenuation and Safety

Mathilde Guerbois, Eugenia Volkova, Naomi L. Forrester, Shannan Rossi, Ilya Frolov, Scott Weaver

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

The live-attenuated TC-83 strain is the only licensed veterinary vaccine available to protect equids against Venezuelan equine encephalitis virus (VEEV) and to protect humans indirectly by preventing equine amplification. However, TC-83 is reactogenic due to its reliance on only two attenuating point mutations and has infected mosquitoes following equine vaccination. To increase its stability and safety, a recombinant TC-83 was previously engineered by placing the expression of the viral structural proteins under the control of the Internal Ribosome Entry Site (IRES) of encephalomyocarditis virus (EMCV), which drives translation inefficiently in insect cells. However, this vaccine candidate was poorly immunogenic. Here we describe a second generation of the recombinant TC-83 in which the subgenomic promoter is maintained and only the capsid protein gene is translated from the IRES. This VEEV/IRES/C vaccine candidate did not infect mosquitoes, was stable in its attenuation phenotype after serial murine passages, and was more attenuated in newborn mice but still as protective as TC-83 against VEEV challenge. Thus, by using the IRES to modulate TC-83 capsid protein expression, we generated a vaccine candidate that combines efficient immunogenicity and efficacy with lower virulence and a reduced potential for spread in nature.

Original languageEnglish (US)
Article numbere2197
JournalPLoS Neglected Tropical Diseases
Volume7
Issue number5
DOIs
StatePublished - May 2013

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Venezuelan Equine Encephalitis Viruses
Capsid Proteins
Vaccines
Safety
Culicidae
Horses
Encephalomyocarditis virus
Viral Structural Proteins
Serial Passage
Point Mutation
Virulence
Insects
Vaccination
Phenotype
Internal Ribosome Entry Sites
Genes

ASJC Scopus subject areas

  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

IRES-driven Expression of the Capsid Protein of the Venezuelan Equine Encephalitis Virus TC-83 Vaccine Strain Increases Its Attenuation and Safety. / Guerbois, Mathilde; Volkova, Eugenia; Forrester, Naomi L.; Rossi, Shannan; Frolov, Ilya; Weaver, Scott.

In: PLoS Neglected Tropical Diseases, Vol. 7, No. 5, e2197, 05.2013.

Research output: Contribution to journalArticle

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