WHO meeting on evaluation of pandemic influenza prototype vaccine in clinical trials, 4-5 May 2006, WHO, Geneva
Summary and meeting documents
On 4-5 May 2006, WHO convened a meeting to:
- Review evaluation of H5N1 pandemic influenza vaccines in clinical trials,
- Review current status of vaccination using alternative routs of vaccine delivery and
- Recommend on research to accelerate availability of effective pandemic vaccines.
Manufacturers reported that production yields of H5 antigen from reference viruses are 30-40% of the average of seasonal influenza viruses, reducing the antigen available in vaccine formulation. There is need to understand the molecular basis of high egg-growth characteristics to improve yield of reverse genetics influenza viruses. All evaluated vaccines were well tolerated. In the USA, non-adjuvanted subvirion vaccine induced levels of antibody acceptable for licensing after two doses of 90 µg H5 antigen. In a concurrent study, intradermal administration of two doses of vaccine containing 45µg of H5 antigen was immunogenic.
Inclusion of aluminium as adjuvant, improved immunogenicity of subvirion vaccines. In Australia, after two doses of unadjuvanted vaccine containing 7.5μg or 15μg of HA, 18% and 34% subjects developed neutralising antibody respectively. Addition of alum induced modest increases in immunogenicity, with 34% and 41% subjects seroconverting respectively. In France, two doses of an aluminium-hydroxide adjuvanted vaccine were immunogenic at 30 µg dose inducing 41% seroconversions by neutralizing antibody. In a clinical trial of MF59-adjuvanted vaccine, third dose induced broadly cross-reactive immune responses to range of H5N1 antigenic variants, suggesting that a priming strategy might be useful against a future pandemic.
Encouraging results were reported from Hungary in a study of aluminium-phosphate whole virus adjuvanted vaccine. A single dose containing 6 µg antigen, induced seroconversions in 68% of vaccinated subjects detected by haemagglutinin-inhibition test. Two culture cell-derived vaccines are in preparation for clinical trials to be initiated at the second half 2006. Live attenuated H5N1 vaccine was tested in animals. One dose of this vaccine demonstrated protective efficacy against lethal challenge with homologous and antigenically distinct H5N1 strains. Candidate vaccine is planned to be submitted to clinical testing in 2006.
Following meeting recommendation WHO decided to organise a consultation on progress in clinical trials of pandemic influenza vaccines to be held on 15-16 February 2007 in Geneva.