Immunogenicity, Safety, and Cross-Reactivity of an Inactivated, Adjuvanted, Prototype Pandemic Influenza (H5N1) Vaccine: A Phase II, Double-Blind, Randomized Trial

Background. Avian influenza A virus H5N1 has the potential to cause a pandemic. Adjuvants and whole-virion vaccines are regarded as antigen sparing for pandemic vaccines. Methods. A double-blind, randomized trial was performed from 28 August to 22 December 2007 in 402 adults; 301 adults were randomly assigned to receive 2 doses of an inactivated, aluminum-adjuvanted, whole-virion H5N1 vaccine containing 5, 10, or 15 mu g of hemagglutinin per dose 28 days apart, and 101 of them received 2 doses of 10 mg of vaccine 14 days apart. The vaccine was manufactured from the recombinant A/Vietman/1194/2004 (NIBRG14) strain. Blood samples were collected for hemagglutination inhibition and microneutralization assays. Results. All formulations were well tolerated, with no serious adverse events. Most local and systemic reactions were mild or moderate. Immune responses were induced after 1 dose in all vaccination groups. The highest immune response was seen after 2 doses of 15 mu g of vaccine, with 90% and 100% seroconversion rates and 90% and 100% of participants having a titer of >= 1: 40 for hemagglutination inhibition and microneutralization assays, respectively. Both the 10- and 15-mu g doses met or exceeded European Union licensure criteria. Generally, higher immune responses were elicited in participants vaccinated 28 days apart than those vaccinated 14 days apart. Cross-reaction assays showed that after 2 doses of 10 mu g of vaccine, 98% and 87% of participants had a microneutralization titer of >= 1: 40 against heterologous Indonesia and Anhui strains, respectively. Conclusions. The inactivated, aluminum-adjuvanted, whole-virion H5N1 vaccine not only showed good immunogenicity and safety but also elicited significant cross-reactivity against heterologous H5N1 strains in clade 2. Trial registration. ClinicalTrials. gov identifier: NCT00535665.