Clinical testing of pre-pandemic live attenuated A/H5N2 influenza candidate vaccine in adult volunteers: results from a placebo-controlled, randomized double-blind phase I study.

BACKGROUND: This study describes a double-blinded randomized placebo-controlled phase I clinical trial of A/H5N2 live attenuated influenza vaccine in healthy volunteers. METHODS: Two doses of vaccine or placebo were administered intranasally to 30 and 10 subjects, respectively. Nasal swabs were examined for vaccine shedding and local antibody responses; serum samples were tested for binding, hemagglutinating and neutralizing antibodies and peripheral blood mononuclear cells were tested for cell-mediated immune responses. RESULTS: The vaccine was well tolerated and not associated with increased rates of adverse events or the occurrence of serious adverse events. Influenza virus was detected in nasal swabs on the first day in the majority of volunteers (93%), while 17% of volunteers tested positive on the second, none on the third day or later following the first vaccination; lower frequency of shedding was observed after the second vaccination. The vaccine was immunogenic as assessed four weeks after the second dose, with 37.9% and 48.3% of subjects seroconverting by hemagglutination inhibition and neutralization assays, respectively. An immune response was observed in 96.6% subjects that received A/H5N2 LAIV in at least one of the assays conducted. None of the placebo recipients exhibited a response in any of the assays. CONCLUSION: The A/H5N2 vaccine was safe, well tolerated, and immunogenic in healthy adults. TRIAL REGISTRATION: ClinicalTrials.gov NCT01719783.