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

Background: The 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). Methods: Healthy 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). Results: Intranasal 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. Conclusions: We show that vaccination with a replication-deficient trivalent influenza vaccine containing HI NI, H3N2 and B strains lacking NS1 is safe and induces significant levels of antibodies (ClinicalTrials.gov identifier NCT01369862). (C) 2013 Elsevier Ltd. All rights reserved.