title: A Single Mutation at PB1 Residue 319 Dramatically Increases the Safety of PR8 Live Attenuated Influenza Vaccine in a Murine Model without Compromising Vaccine Efficacy.
abstract: The live attenuated influenza vaccine (LAIV) is preferentially recommended for use in most children yet remains unsafe for the groups most at risk. Here we have improved the safety of a mouse-adapted live attenuated influenza vaccine containing the same attenuating amino acid mutations as in human LAIV by adding an additional mutation at PB1 residue 319. This results in a vaccine with a 20-fold decrease in protective efficacy and a 10,000-fold increase in safety.
authors.affiliation: Department of Microbiology & Immunology, University of Rochester Medical Center, Rochester, New York, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Cox
authors.affiliation: Department of Microbiology & Immunology, University of Rochester Medical Center, Rochester, New York, USA stephen_dewhurst@urmc.rochester.edu.
authors.forename: Stephen
authors.initials: S
authors.lastname: Dewhurst
mesh_terms: D000818:Animals; D001835:Body Weight; D004195:Disease Models, Animal; D005260:Female; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000235:genetics / Q000276:immunology*; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000473:pathology* / Q000517:prevention & control*; D017354:Point Mutation; D016019:Survival Analysis; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics*; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics*
chemical_list: D007252:Influenza Vaccines; D014613:Vaccines, Attenuated; D014764:Viral Proteins; D037521:Virulence Factors; C077346:influenza virus polymerase basic protein 1