title: Phase I/II trial of a replication-deficient trivalent influenza virus vaccine lacking NS1.
abstract: 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 7.0log10 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 H1N1, H3N2 and B strains lacking NS1 is safe and induces significant levels of antibodies (ClinicalTrials.gov identifier NCT01369862).
authors.affiliation: AVIR Green Hills Biotechnology, 1200 Vienna, Austria. Electronic address: christina_moessler@baxter.com.
authors.forename: Christina
authors.initials: C
authors.lastname: Mössler
authors.forename: Franz
authors.initials: F
authors.lastname: Groiss
authors.forename: Michael
authors.initials: M
authors.lastname: Wolzt
authors.forename: Markus
authors.initials: M
authors.lastname: Wolschek
authors.forename: Joachim
authors.initials: J
authors.lastname: Seipelt
authors.forename: Thomas
authors.initials: T
authors.lastname: Muster
mesh_terms: D000281:Administration, Intranasal; D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000276:immunology; D053122:Influenza A Virus, H3N2 Subtype / Q000235:genetics / Q000276:immunology; D009981:Influenza B virus / Q000235:genetics / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D008297:Male; D010919:Placebos / Q000008:administration & dosage; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology; D017361:Viral Nonstructural Proteins / Q000172:deficiency*
chemical_list: D000914:Antibodies, Viral; C085820:INS1 protein, influenza virus; D007252:Influenza Vaccines; D010919:Placebos; D014613:Vaccines, Attenuated; D017361:Viral Nonstructural Proteins
keywords: Influenza; Intranasal; Live-attenuated; NS1; Reverse genetics; Trivalent