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

J Virol. 2015 Dec 16;90(5):2702-5. doi: 10.1128/JVI.02723-15.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Weight
  • Disease Models, Animal
  • Female
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / adverse effects*
  • Influenza Vaccines / genetics
  • Influenza Vaccines / immunology*
  • Mice
  • Orthomyxoviridae Infections / pathology*
  • Orthomyxoviridae Infections / prevention & control*
  • Point Mutation*
  • Survival Analysis
  • Vaccines, Attenuated / administration & dosage
  • Vaccines, Attenuated / adverse effects
  • Vaccines, Attenuated / genetics
  • Vaccines, Attenuated / immunology
  • Viral Proteins / genetics*
  • Virulence
  • Virulence Factors / genetics*

Substances

  • Influenza Vaccines
  • Vaccines, Attenuated
  • Viral Proteins
  • Virulence Factors
  • influenza virus polymerase basic protein 1