The 5th WHO Meeting on Evaluation of Pandemic Influenza Prototype Vaccines in Clinical Trials, 12-13 February 2009, Geneva
Summary and meeting documents
On 12-13 February 2009, the Department of Initiative for Vaccine Research (IVR) of WHO convened the 4th meeting on “Evaluation of pandemic influenza prototype vaccines in clinical trials”. The objective of the meeting was to compare the immunogenicity of various candidate H5N1 vaccines as determined in recent clinical trials, studying tolerance to the vaccine, dose response and possible antigen-sparing, as well as broadness of the antibody response elicited by each of the available prototype H5N1 vaccines.
Substantial progress has been made over the course of the last year to further assess and characterise prototype pandemic vaccines, particularly with respect to immunogenicity in children and the responses elicited by prime-boost strategies. Among H5N1 vaccines that have been evaluated, the egg derived split/subunit, oil-in-water adjuvanted vaccines have demonstrated dramatic antigen–sparing, cross-clade immune responses, and effective priming.
GlaxoSmithKline’s AS03-adjuvanted H5N1 vaccine is currently licensed by the EMEA and for use in Malaysia and Hong Kong. The MF59-adjuvanted H5N1 vaccine developed by Novartis is being evaluated in phase II trials and Sanofi-Pasteur’s AF03-adjuvanted H5N1 vaccine is undergoing phase II trials. Other market approved H5N1 vaccine formulations include egg–derived, alum-adjuvanted whole or split virus vaccines in Japan (Biken), China ( Sinovac), Australia (CSL). Because oil-in-water preparations have been demonstrated to induce higher homologous and broader heterologous antibody responses than their non-adjuvanted counterparts, studies have been undertaken to apply this adjuvant technology in seasonal influenza vaccination among elderly risk groups. MF59 adjuvanted seasonal vaccines (Fluad; Novartis) has been licensed for use in seasonal vaccines in Europe since 1997. Vaccination of elderly populations with Fluad vaccine reduces significantly hospitalisation rates. GSK is undertaking a multinational phase III trial involving over 35,000 adults aged >65 years to compare the effectiveness of an ASO3-adjuvanted seasonal vaccine to a non-adjuvanted one. Whether these oil-in-water adjuvanted vaccines may provide broadened immune responses and be protective against seasonal drift variants remain to be determined.
Progress continues in evaluating prototype pandemic vaccines in children and the elderly, and the safety and immunogenicity of several H5N1 vaccines has been confirmed for both of these groups. Immunogenicity in children has been demonstrated for alum and several oil-in water adjuvanted vaccines, and trials are ongoing with these and also with Vero cell-derived whole virus vaccines. However, discussions at the meeting lead to an opinion that more data needs to be accumulated, especially in the very young age groups 6 months-3 years. In the event of a pandemic, priority immunisations will likely be targeted at the young, elderly and at risk groups in many countries, so that more data in these groups is needed.
In order to more fully predict the potential protective efficacy of prototype pandemic vaccines, especially those using novel technologies and live-attenuated vaccines, it will be necessary to more fully understand the mechanisms of immunity that confer effective priming and protection against H5N1 and other avian sub-type viruses. Recent studies have shown the potential for two-dose priming regimens to elicit long-term immunologic memory associated with rapid and, in the case of adjuvanted vaccines, broadened antibody responses following heterologous boosting. Studies to examine the efficiency and durability of single dose priming are in progress. Preliminary data presented at this meeting showed virus–specific CD4+ T cells and memory B cells in H5N1 vaccinated individuals. In addition to the development of standardised assays, further research is needed in order to understand how these correlate with protection . Studies in ferrets and perhaps subhuman primates should be a priority research area, as well as human challenge studies where possible. Considerable resources are required for such studies but their results could prove critical in informing future research directions and vaccine policies. The standardisation of already established serological assays, like the first internationally accepted anti-H5 clade 1 antiserum standard, is also necessary in order to cross-compare vaccine trial outcomes.
Last updated: 6 April 2009
Last updated: 6 April 2009