WARF: P09022US02

Attenuated Influenza Viruses for Development of Live Influenza Vaccine


Yoshihiro Kawaoka, Hatice Akarsu, Kiyoko Horimoto

The Wisconsin Alumni Research Foundation (WARF) is seeking commercial partners interested in attenuated influenza virus strains with mutations in the influenza A virus nuclear export protein.
OVERVIEWInfluenza is a major disease in humans that can be prevented by vaccination. Because new epidemic strains arise every year or two, influenza vaccines must be adapted almost every year.  Live attenuated vaccines, which contain pathogens that have been modified so they no longer cause disease, generally induce a more effective immune response than other types of vaccines.

A UW-Madison researcher previously developed attenuated influenza virus strains with mutations in the ion channel protein M2 and the surface-exposed membrane channel protein NB (see WARF reference numbers P00235US and P03251US).  These strains may be useful in the production of live influenza vaccines. 
THE INVENTIONUW-Madison researchers now have developed new mutated influenza viruses that grow normally in cell culture but whose growth is attenuated in mice.  These viruses are useful for vaccines and vaccine production.

The mutations are in the influenza A virus nuclear export protein, known as NEP or NS2.  Because the NS genes are highly conserved, they likely mutate less frequently than other influenza genes, making viruses with NS2 mutations ideal for the development of live attenuated vaccines. 
  • Live influenza vaccines
  • Vaccine development
  • Mutated influenza strains are attenuated in mice.
  • Mutations do not affect virus replication in cell culture.
  • NS genes are highly conserved and may mutated less frequently than viral genes/proteins under selection pressure, such as hemagglutinin (HA), neuraminidase (NA) or the ion channel protein M2. 
  • Vaccines prepared from live, attenuated virus are less costly than vaccines prepared from inactivated virus, and induce an immunity that generally is more durable, effective and cross-reactive.
STAGE OF DEVELOPMENTMice inoculated with these mutated viruses experienced no weight loss, while 50 percent of mice given the wild-type virus died within nine days. Mice immunized with one of the mutant strains were later challenged with wild-type virus. All of the immunized mice survived and contained no virus.
Contact Information
For current licensing status, please contact Jennifer Gottwald at or 608-960-9854.
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