Clinical Studies of Vaccines for Pandemic Influenza

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We have generated candidate vaccines against H9N2, H5N1 and H7N3 influenza viruses. Based on promising preclinical data in mice and ferrets, clinical lots of these vaccines were generated for Phase I clinical trials of the safety and immunogenicity of the vaccines for healthy adults under an IND. H9N2 cold-adapted (ca) vaccine: A Phase I study was initiated in 50 healthy adults who were admitted to an in-patient unit. The vaccine was safe and well tolerated but the level of replication was low. Despite this, the H9N2 ca vaccine induced serum antibody in over 90% of seronegative subjects who received two doses of vaccine. H5N1 cold-adapted (ca) vaccines: Three candidate vaccines were developed based on H5N1 viruses isolated in 1997, 2003 and 2004. In each virus, the HA and NA genes were derived from wild-type H5N1 viruses. The HA in each case was modified to remove the multibasic amino acid cleavage site that is a virulence motif. A Phase I trial for safety, infectivity, and immunogenicity of the 2004 H5N1 Vaccine based on the A/VietNam/1203/2004 (H5N1) virus, was undertaken at a dose of 106.7 TCID50 per dose in 20 healthy adults, aged 18-49 years. The clinical trial was conducted in an isolation unit. Subjects received two doses of vaccine, administered 28 to 62 days apart, and were sequestered in an isolation unit 3 weeks following both doses. The level of replication, infectivity, and immunogenicity of the vaccine virus at this dose were low. Therefore, a study was undertaken to evaluate the safety, infectivity and immunogenicity of a moderately higher dose (107.5 TCID50) of the same vaccine. Nineteen subjects received two doses of this dose. The vaccine was safe & well tolerated. Analysis of data from this study is in progress. In order to determine whether the finding of low infectivity and low immunogenicity observed with the 2004 H5N1 ca virus was unique to this strain, a Phase I study was undertaken with the 2003 H5N1 ca vaccine. Sixteen subjects received 2 doses of the 2003 H5N1 ca vaccine. The study is in progress. H7N3 cold-adapted (ca) vaccine: Based on promising preclinical data in mice and ferrets, an IND was submitted for a Phase I study to evaluate safety, level of replication, infectivity and immunogenicity of an H7N3 ca vaccine based on A/chicken/British Columbia/CN-6/2004 (H7N3). The study will be initiated in September 2007.