The fourth meeting on influenza vaccines that induce broad spectrum and long-lasting immune responses, London, 9-10 November 2009
Summary and meeting documents
On 9-10 November 2009, the Initiative for Vaccine Research (IVR) of the World Health Organization and the Wellcome Trust convened the fourth meeting on “Influenza vaccines that induce broad spectrum and long-lasting immune responses” as a follow-up to three previous meetings held in 2004-2007. The objectives of the meeting were to review the current status of research in the area of influenza vaccine strategies able to induce broad spectrum and long-lasting immune responses and to provide cross-protection against influenza viruses from the same or different subtypes. These new vaccines would, thus, overcome one of the problems with the current vaccination strategy based on annual intervention and be more acceptable in developing countries. These vaccines would also contribute to the control of epidemic situations and potential pandemics.
Recognized correlates of immune protection, and a standardised approach to their measurement, are critical for the assessment and regulatory approval of novel influenza vaccines. Ideal vaccines should be safe and stimulate all components of the immune system including long-lasting, cross-reactive neutralising antibodies, cytotoxic lymphocytes (CTL) and helper T cells, as well as mucosal responses. A series of presentations reviewed known and exploratory mechanisms of humoral and cellular immune protection against influenza virus infection. Understanding of the relative importance of mucosal antibodies and T cell responses in protection against influenza virus infection and related illness is considered as important for the prediction of efficacy of candidate vaccines. Moreover, assessment of the longevity of immune responses induced by influenza vaccines is critical for determining the interval needed between booster doses, but is complicated in humans by immune responses induced by recurrent natural infections.
Results obtained in different settings have shown that school-based vaccination with live attenuated influenza vaccines (LAIV) induces significant reduction in overall acute respiratory illness (ARI) rates in intervention areas among different age groups, suggesting that lower circulation of influenza virus among vaccinated children reduces the exposure of older people. New candidate LAIVs are currently under development. These vaccines induce protection in animal models against homologous and antigenically distinct heterologous influenza virus challenge infection, and further studies in the area are encouraged.
Considerable progress was achieved in the development and evaluation of adjuvanted influenza vaccines. Previous experience with AS03-adjuvanted egg-derived, split virion H5N1 vaccine, leading to European marketing authorization for this product, facilitated rapid pandemic A(H1N1) 2009 vaccine development and registration. MF59-adjuvanted influenza vaccines, formulated as monovalent H5N1 or tetravalent seasonal vaccine with addition of an H5N1 valency (H5N1, H3N2, H1N1 and B), were used in various prime-boost schedules. No differences were observed in serologic responses, regardless of the vaccine combination.
In the session on new technologies for the development of novel influenza vaccines, data was presented and discussed on the following approaches: virus – like particle (VLP)-based vaccines, live viral vectors, M2e-based vaccines, novel production methods, and novel delivery systems. At present, little is known on the potential protective efficacy of most of these new types of vaccines in humans, and much more has to be learnt on their immunogenicity and principal characteristics before they can be registered for human use. However, if successful, these new technologies could bring forward the goal of a universal influenza vaccine