A new approach to an influenza live vaccine: modification of the cleavage site of hemagglutinin.
A promising approach to reduce the impact of influenza is the use of an attenuated, live virus as a vaccine. Using reverse genetics, we generated a mutant of strain A/WSN/33 with a modified cleavage site within its hemagglutinin, which depends on proteolytic activation by elastase. Unlike the wild-type, which requires trypsin, this mutant is strictly dependent on elastase. Both viruses grow equally well in cell culture. In contrast to the lethal wild-type virus, the mutant is entirely attenuated in mice. At a dose of 10(5) plaque-forming units, it induced complete protection against lethal challenge. This approach allows the conversion of any epidemic strain into a genetically homologous attenuated virus.
Stech
J
J
Institut fuer Virologie, Klinikum der Philipps-Universitaet Marburg, Postfach 2360, 35011 Marburg, Germany. stech@med.uni-marburg.de
Garn
H
H
Wegmann
M
M
Wagner
R
R
Klenk
H-D
HD
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D002460:Cell Line; D004285:Dogs; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009980:Influenza A virus / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D007252:Influenza Vaccines; D007251:Influenza, Human / Q000401:mortality / Q000821:virology; D008168:Lung / Q000821:virology; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010196:Pancreatic Elastase / Q000378:metabolism; D014613:Vaccines, Attenuated; D010948:Viral Plaque Assay; D014779:Virus Replication
D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D014613:Vaccines, Attenuated; D010196:Pancreatic Elastase