A new approach to an influenza life vaccine: haemagglutinin cleavage site mutants generated by reverse genetics.
A promising approach to reduce the impact of influenza is the use of an attenuated life virus as a vaccine. Using reverse genetics, a mutant of strain A/WSN/33 with a modified cleavage site within its haemagglutinin was generated which depends on proteolytic activation by elastase. Unlike the wild-type requiring trypsin, this mutant is strictly dependent on elastase. Both viruses grow equally well in cell culture in the presence of the respective protease. In contrast to the lethal wild-type, the mutant is entirely attenuated in mice at a virus dose of 10(6) pfu. At a dose of 10(5) pfu it induced complete protection against lethal challenge. This approach allows the conversion of any epidemic strain into a genetically homologous attenuated virus.
Stech
Jürgen
J
Institut für Virologie, Universitätsklinikum Giessen und Marburg, Germany. stech@staff.uni-marburg.de
Klenk
Hans-Dieter
HD
D000818:Animals; D006388:Hemagglutinins / Q000235:genetics* / Q000276:immunology; D006801:Humans; D009980:Influenza A virus / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity; D007252:Influenza Vaccines / Q000235:genetics; D007251:Influenza, Human / Q000517:prevention & control* / Q000821:virology*; D051379:Mice; D016297:Mutagenesis, Site-Directed / Q000379:methods; D009154:Mutation / Q000235:genetics; D010196:Pancreatic Elastase / Q000502:physiology; D014613:Vaccines, Attenuated / Q000235:genetics
D006388:Hemagglutinins; D007252:Influenza Vaccines; D014613:Vaccines, Attenuated; D010196:Pancreatic Elastase