Immunogenicity, safety, and cross-reactivity of an inactivated, adjuvanted, prototype pandemic influenza (H5N1) vaccine: a phase II, double-blind, randomized trial

Abstract

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 microg of hemagglutinin per dose 28 days apart, and 101 of them received 2 doses of 10 microg 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 microg of vaccine, with 90% and 100% seroconversion rates and 90% and 100% of participants having a titer of > or = 1:40 for hemagglutination inhibition and microneutralization assays, respectively. Both the 10- and 15-microg 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 microg of vaccine, 98% and 87% of participants had a microneutralization titer of > or = 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.