Abstract
BackgroundPathogenic avian influenza virus (H5N1) has the potential to cause a major global pandemic in humans. Safe and effective vaccines that induce immunologic memory and broad heterotypic response are needed.Methods and FindingsHealthy adults aged 18–60 and >60 years (n = 313 and n = 173, respectively) were randomized (1∶1) to receive two primary and one booster injection of 7.5 μg or 15 μg doses of a subunit MF59-adjuvanted H5N1 (A/Vietnam/1194/2004) (clade 1) vaccine. Safety was monitored until 6 months after booster. Immunogenicity was assessed by hemagglutination inhibition (HI), single radial hemolysis (SRH) and microneutralization assays (MN). Mild injection-site pain was the most common adverse reaction. No serious adverse events relating to the vaccine were reported. The humoral immune responses to 7.5 μg and 15 μg doses were comparable. The rates for seroprotection (HI>40; SRH>25mm2; MN ≥40) after the primary vaccination ranged 72–87%. Six months after primary vaccination with the 7.5 μg dose, 18% and 21% of non-elderly and elderly adults were seroprotected; rates increased to 90% and 84%, respectively, after the booster vaccination. In the 15 μg group, seroprotection rates among non-elderly and elderly adults increased from 25% and 62% after primary vaccination to 92% and 88% after booster vaccination, respectively. A heterologous immune response to the H5N1/turkey/Turkey/05 strain was elicited after second and booster vaccinations.ConclusionsBoth formulations of MF59-adjuvanted influenza H5N1 vaccine were well tolerated. The European Union requirement for licensure for pre-pandemic vaccines was met by the lower dose tested. The presence of cross-reactive antibodies to a clade 2 heterologous strain demonstrates that this vaccine may be appropriate for pre-pandemic programs.Trial RegistrationClinicalTrials.gov NCT00311480
Highlights
The highly pathogenic avian influenza H5N1 virus, first reported in China in 1996, is responsible for severe avian influenza outbreaks [1,2,3]
The presence of cross-reactive antibodies to a clade 2 heterologous strain demonstrates that this vaccine may be appropriate for pre-pandemic programs
One study found that two 30 mg doses of an alum-adjuvanted split-virion H5N1 vaccine were needed to induce an immune response that met two of three criteria for European Union licensure [12]
Summary
The highly pathogenic avian influenza H5N1 virus, first reported in China in 1996, is responsible for severe avian influenza outbreaks [1,2,3]. Since the amount of antigen in both these cases is substantially more than is needed for protection against seasonal influenza strains, and given current limits on worldwide vaccine production capacity, measures to increase the immune response and reduce the antigen content are essential. This is important as clinical trials of H5N1 vaccines have shown that two doses of adjuvanted vaccine are necessary to satisfy all European regulatory criteria for immunogenicity [12,13,14]. Safe and effective vaccines that induce immunologic memory and broad heterotypic response are needed
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