title: Stability of RNA virus attenuation approaches.
abstract: The greatest risk from live-attenuated vaccines is reversion to virulence. Particular concerns arise for RNA viruses, which exhibit high mutation frequencies. We examined the stability of 3 attenuation strategies for the alphavirus, Venezuelan equine encephalitis virus (VEEV): a traditional, point mutation-dependent attenuation approach exemplified by TC-83; a rationally designed, targeted-mutation approach represented by V3526; and a chimeric vaccine, SIN/TC/ZPC. Our findings suggest that the chimeric strain combines the initial attenuation of TC-83 with the greater phenotypic stability of V3526, highlighting the importance of the both initial attenuation and stability for live-attenuated vaccines.
authors.affiliation: Institute for Human Infections and Immunity, Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Joan L
authors.initials: JL
authors.lastname: Kenney
authors.forename: Sara M
authors.initials: SM
authors.lastname: Volk
authors.forename: Jyotsna
authors.initials: J
authors.lastname: Pandya
authors.forename: Eryu
authors.initials: E
authors.lastname: Wang
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Liang
authors.forename: Scott C
authors.initials: SC
authors.lastname: Weaver
mesh_terms: D000818:Animals; D004666:Encephalitis Virus, Venezuelan Equine / Q000235:genetics* / Q000472:pathogenicity; D004685:Encephalomyelitis, Venezuelan Equine / Q000517:prevention & control; D016679:Genome, Viral; D042822:Genomic Instability; D051379:Mice; D010641:Phenotype; D017354:Point Mutation; D012367:RNA, Viral / Q000235:genetics; D017423:Sequence Analysis, RNA; D014613:Vaccines, Attenuated / Q000235:genetics* / Q000276:immunology; D010948:Viral Plaque Assay; D014765:Viral Vaccines / Q000235:genetics* / Q000276:immunology; D014774:Virulence
chemical_list: D012367:RNA, Viral; D014613:Vaccines, Attenuated; D014765:Viral Vaccines