MF59®-Adjuvanted H5N1 Vaccine Induces Immunologic Memory and Heterotypic Antibody Responses in Non-Elderly and Elderly Adults

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

Passive surveillance of adverse events of an MF59-adjuvanted H1N1v vaccine during the pandemic mass vaccinations

“…[12][13][14] Previous clinical studies have demonstrated that an MF59-adjuvanted seasonal trivalent influenza vaccine induced higher and broader antibody responses compared with nonadjuvanted vaccines, especially in subjects with low prevaccination antibody titers and with a confirmed safety profile in vulnerable populations, including the elderly, those with underlying chronic conditions and children. 9,[12][13][14][15][16][17][18][19][20][21][22][23] The EMA had initially recommended a 2-dose administration schedule at least 21 days apart for the centrally authorized pandemic vaccines based on existing data from H5N1 vaccines. 24,25 Subsequently published immunogenicity and safety data from H1N1v clinical trials demonstrated that the administration of a single dose of vaccine would be sufficient to elicit robust immune responses that comply with international licensing criteria.…”

Adjuvanticity of the oil-in-water emulsion MF59 is independent of Nlrp3 inflammasome but requires the adaptor protein MyD88

“…MF59 has been licensed in Europe as well for pandemic influenza vaccines and has been widely used for the 2009 H1N1 pandemic flu campaign (16). Clinical trials conducted using avian H5 pandemic flu antigens have demonstrated that MF59 allowed for antigen dose sparing and increased seroconversion and cross-protection in vaccinees (17). A recent study has shown that in infants MF59 increases the efficacy of the Trivalent Inactivated influenza Vaccine from 43% to 89%.…”

Assessment of squalene adjuvanted and non-adjuvanted vaccines against pandemic H1N1 influenza in children 6 months to 17 years of age

“…against H5N1, two-dose vaccination schedules were needed, irrespective of adjuvant content. [8][9][10] The hemagglutinin of the influenza virus causing the 2009 pandemic was derived from the 1918 influenza A strain that entered swine around that time.…”

“…Squalene-based emulsion adjuvants had been used to enhance the immunogenicity of the poorly immunogenic H5N1 avian influenza virus vaccines in various age groups, [8][9][10] as well as seasonal influenza vaccines for the elderly and young children who…”