Phase I/II trial of a replication-deficient trivalent influenza virus vaccine lacking NS1

•We performed the first in man study with a live replication-deficient delNS1-trivalent vaccine.•Significant antibody titers to influenza strains contained in the vaccine were induced.•Seroconversion occurred most frequently in participants who were seronegative before vaccination.•A single intranasal dose was well tolerated and safe in healthy male and female participants.•No vaccine virus could be re-isolated in volunteers after immunization.

BackgroundThe non-structural protein NS1 of the influenza virus counteracts the interferon-mediated immune response of the host. We investigated the safety and immunogenicity of a trivalent formulation containing influenza H1N1, H3N2 and B strains lacking NS1 (delNS1-trivalent).MethodsHealthy adult study participants who were seronegative for at least one strain present in the vaccine formulation were randomized to receive a single intranasal dose of delNS1-trivalent vaccine at 7.0 log10 TCID50/subject (n = 39) or placebo (n = 41).ResultsIntranasal vaccination with the live replication-deficient delNS1-trivalent vaccine was well tolerated with no treatment-related serious adverse events. The most common adverse events identified, i.e. headache, oropharyngeal pain and rhinitis-like symptoms, were mainly mild and transient and distributed similarly in the treatment and placebo groups. Significant vaccine-specific immune responses were induced. Pre-existing low antibody titers or seronegativity for the corresponding vaccine strain yielded better response rates.ConclusionsWe show that vaccination with a replication-deficient trivalent influenza vaccine containing H1N1, H3N2 and B strains lacking NS1 is safe and induces significant levels of antibodies (ClinicalTrials.gov identifier NCT01369862).