Oral administration of an adenovirus vector encoding both an avian influenza A hemagglutinin and a TLR3 ligand induces antigen specific granzyme B and IFN-γ T cell responses in humans

Vaccine. 2013 Mar 25;31(13):1752-8. doi: 10.1016/j.vaccine.2013.01.023. Epub 2013 Jan 25.

Abstract

Purpose: To test the safety and immunogenicity of an orally delivered avian influenza vaccine. The vaccine has a non-replicating adenovirus type 5 vector backbone which expresses hemagglutinin from avian influenza and a TLR3 ligand as an adjuvant.

Methods: Forty-two subjects were randomized into 3 groups dosed with either 1×10(10), 1×10(9), or 1×10(8) IU of the vaccine administered in capsules. Twelve subjects were vaccinated with identical capsules containing placebo. A portion of the 1×10(9) dose group were immunized a second time 4 weeks after the first immunization. The safety of the vaccine was assessed by measuring the frequency and severity of adverse events in placebo versus vaccine treated subjects. IFN-γ and granzyme B ELISpot assays were used to assess immunogenicity.

Results: The vaccine had a positive safety profile with no treatment emergent adverse events reported above grade 1, and with an adverse event frequency in the treated groups no greater than placebo. Antigen specific cytotoxic and IFN-γ responses were induced in a dose dependent manner and cytotoxic responses were boosted after a second vaccination.

Conclusion: This first in man clinical trial demonstrates that an orally delivered adenovirus vectored vaccine can induce immune responses to antigen with a favorable safety profile.

Clinical trial registration number: NCT01335347.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adenoviridae / genetics*
  • Administration, Oral
  • Adult
  • Animals
  • Drug Carriers / administration & dosage*
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Drug-Related Side Effects and Adverse Reactions / pathology
  • Enzyme-Linked Immunospot Assay
  • Female
  • Genetic Vectors
  • Granzymes / metabolism
  • Hemagglutinin Glycoproteins, Influenza Virus / genetics
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology*
  • Humans
  • Influenza Vaccines / administration & dosage*
  • Influenza Vaccines / adverse effects
  • Influenza Vaccines / genetics
  • Influenza Vaccines / immunology*
  • Influenza, Human / prevention & control
  • Interferon-gamma / metabolism
  • Male
  • Placebos / administration & dosage
  • T-Lymphocytes / immunology*
  • Toll-Like Receptor 3 / agonists*
  • Toll-Like Receptor 3 / genetics

Substances

  • Drug Carriers
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Influenza Vaccines
  • Placebos
  • TLR3 protein, human
  • Toll-Like Receptor 3
  • Interferon-gamma
  • Granzymes

Associated data

  • ClinicalTrials.gov/NCT01335347