title: Live attenuated influenza virus vaccines by computer-aided rational design.
abstract: Despite existing vaccines and enormous efforts in biomedical research, influenza annually claims 250,000-500,000 lives worldwide, motivating the search for new, more effective vaccines that can be rapidly designed and easily produced. We applied the previously described synthetic attenuated virus engineering (SAVE) approach to influenza virus strain A/PR/8/34 to rationally design live attenuated influenza virus vaccine candidates through genome-scale changes in codon-pair bias. As attenuation is based on many hundreds of nucleotide changes across the viral genome, reversion of the attenuated variant to a virulent form is unlikely. Immunization of mice by a single intranasal exposure to codon pair-deoptimized virus conferred protection against subsequent challenge with wild-type (WT) influenza virus. The method can be applied rapidly to any emerging influenza virus in its entirety, an advantage that is especially relevant when dealing with seasonal epidemics and pandemic threats, such as H5N1- or 2009-H1N1 influenza.
authors.affiliation: Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York, USA. smueller@ms.cc.sunysb.edu
authors.forename: Steffen
authors.initials: S
authors.lastname: Mueller
authors.forename: J Robert
authors.initials: JR
authors.lastname: Coleman
authors.forename: Dimitris
authors.initials: D
authors.lastname: Papamichail
authors.forename: Charles B
authors.initials: CB
authors.lastname: Ward
authors.forename: Anjaruwee
authors.initials: A
authors.lastname: Nimnual
authors.forename: Bruce
authors.initials: B
authors.lastname: Futcher
authors.forename: Steven
authors.initials: S
authors.lastname: Skiena
authors.forename: Eckard
authors.initials: E
authors.lastname: Wimmer
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003062:Codon; D017076:Computer-Aided Design; D004285:Dogs; D016679:Genome, Viral; D007928:Lethal Dose 50; D051379:Mice; D008969:Molecular Sequence Data; D009975:Orthomyxoviridae / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines
chemical_list: D003062:Codon; D014765:Viral Vaccines