title: Chimeric alphavirus vaccine candidates protect mice from intranasal challenge with western equine encephalitis virus.
abstract: We developed two types of chimeric Sindbis virus (SINV)/western equine encephalitis virus (WEEV) alphaviruses to investigate their potential use as live virus vaccines against WEE. The first-generation vaccine candidate, SIN/CO92, was derived from structural protein genes of WEEV strain CO92-1356, and two second-generation candidates were derived from WEEV strain McMillan. For both first- and second-generation vaccine candidates, the nonstructural protein genes were derived from SINV strain AR339. Second-generation vaccine candidates SIN/SIN/McM and SIN/EEE/McM included the envelope glycoprotein genes from WEEV strain McMillan; however, the amino-terminal half of the capsid, which encodes the RNA-binding domain, was derived from either SINV or eastern equine encephalitis virus (EEEV) strain FL93-939. All chimeric viruses replicated efficiently in mammalian and mosquito cell cultures and were highly attenuated in 6-week-old mice. Vaccinated mice developed little or no detectable disease and showed little or no evidence of challenge virus replication; however, all developed high titers of neutralizing antibodies. Upon intranasal challenge with high doses of virulent WEEV strains, mice vaccinated with >or=10(5)PFU of SIN/CO92 or >or=10(4)PFU of SIN/SIN/McM or SIN/EEE/McM were completely protected from disease. These findings support the potential use of these live-attenuated vaccine candidates as safe and effective vaccines against WEE.
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Atasheva
authors.forename: Eryu
authors.initials: E
authors.lastname: Wang
authors.forename: A Paige
authors.initials: AP
authors.lastname: Adams
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Plante
authors.forename: Sai
authors.initials: S
authors.lastname: Ni
authors.forename: Katherine
authors.initials: K
authors.lastname: Taylor
authors.forename: Mary E
authors.initials: ME
authors.lastname: Miller
authors.forename: Ilya
authors.initials: I
authors.lastname: Frolov
authors.forename: Scott C
authors.initials: SC
authors.lastname: Weaver
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002460:Cell Line; D006224:Cricetinae; D004667:Encephalitis Virus, Western Equine / Q000235:genetics / Q000276:immunology*; D004683:Encephalomyelitis, Equine / Q000517:prevention & control*; D005260:Female; D005822:Genetic Vectors; D016679:Genome, Viral; D051379:Mice; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D011247:Pregnancy; D011995:Recombination, Genetic; D017422:Sequence Analysis, DNA; D012845:Sindbis Virus / Q000235:genetics*; D016019:Survival Analysis; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000276:immunology; D015678:Viral Structural Proteins / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D014613:Vaccines, Attenuated; D017361:Viral Nonstructural Proteins; D015678:Viral Structural Proteins; D014765:Viral Vaccines