tetano
Editor, Senior Moderator
J Virol. 2015 Aug 12. pii: JVI.01443-15. [Epub ahead of print]
[h=1]Generation of live attenuated influenza virus using codon usage bias.[/h] Fan RL[SUP]1[/SUP], Valkenburg SA[SUP]1[/SUP], Wong CK[SUP]1[/SUP], Li OT[SUP]1[/SUP], Nicholls JM[SUP]2[/SUP], Rabadan R[SUP]3[/SUP], Peiris JS[SUP]1[/SUP], Poon LL[SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Seasonal influenza epidemics and occasional pandemics threaten public health worldwide. New alternative strategies for generating recombinant viruses of vaccine potential are needed. Interestingly, influenza viruses circulating in different hosts have been found to have distinct codon usage patterns, which may reflect host adaptation. We therefore hypothesized that it is possible to make a human seasonal influenza virus that is specifically attenuated in human cells, but not in eggs, by converting its codon usage similar to those observed from avian influenza viruses. This approach might help to generate human live attenuated viruses without affecting their yield in eggs. To test this hypothesis, over 300 silent mutations were introduced into the genome of a seasonal H1N1 influenza virus. The resultant mutant was significantly attenuated in mammalian cells and mice, yet it grew well in embryonated eggs. A single dose of intranasal vaccination induced potent innate, humoral and cellular immune responses, and the mutant could protect mice against homologous and heterologous viral challenges. The attenuated mutant could also be used as a vaccine master donor strain by introducing hemagglutinin and neuraminidase genes derived from other strains. Thus our approach is a successful strategy to generate attenuated viruses for future vaccine application.
[h=4]IMPORTANCE:[/h] Vaccination has been one of the best protective measures in combating influenza infection. Current licensed influenza vaccines and their production have various limitations. Our virus attenuation strategy makes use of codon usage biases of human and avian influenza viruses to generate a human-derived influenza virus that is attenuated in mammalian hosts. This method, however, does not affect the virus replication in eggs. This makes the resultant mutants highly compatible with existing egg-based vaccine production pipelines. The viral proteins generated from the codon bias mutants are identical to the wild-type viral proteins. In addition, our massive genome-wide mutational approach further minimizes the concern of reverse mutations. The potential use of this kind of codon bias mutants as a master donor strain to generate other live attenuated viruses is also demonstrated. These findings put forward a promising live attenuated influenza vaccine generation strategy to control influenza.
Copyright ? 2015, American Society for Microbiology. All Rights Reserved.
PMID: 26269186 [PubMed - as supplied by publisher]
[h=1]Generation of live attenuated influenza virus using codon usage bias.[/h] Fan RL[SUP]1[/SUP], Valkenburg SA[SUP]1[/SUP], Wong CK[SUP]1[/SUP], Li OT[SUP]1[/SUP], Nicholls JM[SUP]2[/SUP], Rabadan R[SUP]3[/SUP], Peiris JS[SUP]1[/SUP], Poon LL[SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Seasonal influenza epidemics and occasional pandemics threaten public health worldwide. New alternative strategies for generating recombinant viruses of vaccine potential are needed. Interestingly, influenza viruses circulating in different hosts have been found to have distinct codon usage patterns, which may reflect host adaptation. We therefore hypothesized that it is possible to make a human seasonal influenza virus that is specifically attenuated in human cells, but not in eggs, by converting its codon usage similar to those observed from avian influenza viruses. This approach might help to generate human live attenuated viruses without affecting their yield in eggs. To test this hypothesis, over 300 silent mutations were introduced into the genome of a seasonal H1N1 influenza virus. The resultant mutant was significantly attenuated in mammalian cells and mice, yet it grew well in embryonated eggs. A single dose of intranasal vaccination induced potent innate, humoral and cellular immune responses, and the mutant could protect mice against homologous and heterologous viral challenges. The attenuated mutant could also be used as a vaccine master donor strain by introducing hemagglutinin and neuraminidase genes derived from other strains. Thus our approach is a successful strategy to generate attenuated viruses for future vaccine application.
[h=4]IMPORTANCE:[/h] Vaccination has been one of the best protective measures in combating influenza infection. Current licensed influenza vaccines and their production have various limitations. Our virus attenuation strategy makes use of codon usage biases of human and avian influenza viruses to generate a human-derived influenza virus that is attenuated in mammalian hosts. This method, however, does not affect the virus replication in eggs. This makes the resultant mutants highly compatible with existing egg-based vaccine production pipelines. The viral proteins generated from the codon bias mutants are identical to the wild-type viral proteins. In addition, our massive genome-wide mutational approach further minimizes the concern of reverse mutations. The potential use of this kind of codon bias mutants as a master donor strain to generate other live attenuated viruses is also demonstrated. These findings put forward a promising live attenuated influenza vaccine generation strategy to control influenza.
Copyright ? 2015, American Society for Microbiology. All Rights Reserved.
PMID: 26269186 [PubMed - as supplied by publisher]