Author: ["J Stech","H Garn","M Wegmann","R Wagner","H-D Klenk"]
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Abstract
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 105 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.Cite this article
Stech, J., Garn, H., Wegmann, M. et al. A new approach to an influenza live vaccine: modification of the cleavage site of hemagglutinin. Nat Med 11, 683–689 (2005). https://doi.org/10.1038/nm1256 