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

Vaccine. 2013 Dec 16;31(52):6194-200. doi: 10.1016/j.vaccine.2013.10.061. Epub 2013 Oct 30.

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).

Keywords: Influenza; Intranasal; Live-attenuated; NS1; Reverse genetics; Trivalent.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Adolescent
  • Adult
  • Antibodies, Viral / blood
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Drug-Related Side Effects and Adverse Reactions / pathology
  • Female
  • Healthy Volunteers
  • Humans
  • Influenza A Virus, H1N1 Subtype / genetics
  • Influenza A Virus, H1N1 Subtype / immunology
  • Influenza A Virus, H3N2 Subtype / genetics
  • Influenza A Virus, H3N2 Subtype / immunology
  • Influenza B virus / genetics
  • Influenza B virus / immunology
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / adverse effects*
  • Influenza Vaccines / immunology*
  • Male
  • Placebos / administration & dosage
  • Vaccines, Attenuated / administration & dosage
  • Vaccines, Attenuated / immunology
  • Viral Nonstructural Proteins / deficiency*

Substances

  • Antibodies, Viral
  • INS1 protein, influenza virus
  • Influenza Vaccines
  • Placebos
  • Vaccines, Attenuated
  • Viral Nonstructural Proteins

Associated data

  • ClinicalTrials.gov/NCT01369862