7th WHO Meeting on Evaluation of Pandemic Influenza Vaccines in Clinical Trials, 17-18 February 2011, Geneva
Summary and meeting documents
Although public health concerns over the 2009 H1N1 pandemic have subsided, improved pandemic influenza vaccines remain a major interest of the World Health Organization (WHO). On February 17-18, 2011, the World Health Organization convened the 7th meeting on “the Evaluation of pandemic influenza vaccines in clinical trials” to review the progress made on pandemic A (H1N1) 2009 vaccines and the evaluation of their effectiveness in the field, especially in children less than 3 years of age and in pregnant women. Other topics to be addressed included a comparison of egg- and cell culture-based influenza vaccines, technical issues related to vaccine strain development and vaccine potency, and the status of development of prototype influenza vaccines using new technologies.
Pandemic A (H1N1) vaccines were safe in young children, pregnant women and immunocompromized individuals. Overall effectiveness of inactivated A (H1N1) vaccines for all ages was found to vary between 72% and 100% in different countries and with different vaccine preparations. Effectiveness of pandemic A (H1N1) 2009 live attenuated vaccine was estimated to be approximately 80% in pediatric populations in the USA. A single dose of inactivated vaccine adjuvanted with AS03, MF59 or AF03 induced protective immunity in young children and pregnant women. However, unadjuvanted vaccines as well as low dose adjuvanted vaccines (1.9 µg HA) required two doses to elicit protective antibody levels in these populations.
Vaccine effectiveness, however, was found to be substantially lower in HIV-infected persons, especially those with less than 200 CD4+ T-cells/µL. The finding that HIV-infected persons generated significantly poorer antibody responses to influenza A (H1N1) vaccines compared with HIV-uninfected persons was documented in several studies, independent of whether the inactivated vaccine used was adjuvanted or not. The rate of seroconversion could be increased significantly by administration of a second dose of vaccine, or by simultaneous administration of the pandemic vaccine and a seasonal vaccine, or by doubling the dose of HA (30 µg) in the vaccine. Poor immunogenicity results were similarly observed in organ transplant recipients, who are kept under immunosuppressive treatment.
Pandemic LAIV was licensed for use in the USA, Russia and India. Since evaluation of immunogenicity by traditional HAI antibody assays are not an appropriate surrogate marker for protection afforded by LAIV, there is an urgent need to develop and standardize immunogenicity assays that measure and predict protection by this type of vaccine.
Clinical trials of pandemic H1N1 vaccines produced by new manufacturers in emerging countries also showed good results in terms of safety and immunogenicity, highlighting the remarkable progress made in establishing new worldwide facilities for the production of influenza vaccines.
Clinical evaluation of influenza vaccines developed using new technologies showed they were well tolerated and induced antibody and/or T cell immune responses to viral proteins. Further studies are warranted to validate novel immunological criteria for evaluation and licensing of such new influenza vaccine concepts. On the regulatory side, work should be undertaken to harmonize the results of serological tests used to evaluate the immunogenicity of traditional influenza vaccines.