Recombinant influenza virus carrying human adenovirus epitopes elicits protective immunity in mice

Antiviral Res. 2015 Sep:121:145-51. doi: 10.1016/j.antiviral.2015.06.015. Epub 2015 Jun 23.

Abstract

Human adenoviruses (HAdVs) are known to cause a broad spectrum of diseases in pediatric and adult patients. As this time, there is no specific therapy for HAdV infection. This study used reverse genetics (RG) to successfully rescue a recombinant influenza virus, termed rFLU/HAdV, with the HAdV hexon protein antigenic epitope sequence inserted in the influenza non-structural (NS1) protein gene. rFLU/HAdV morphological characteristics were observed using electron microscopy. Furthermore, BALB/c mice immunized twice intranasally (i.n.) with 10(4) TCID50 or 10(5) TCID50 rFLU/HAdV showed robust humoral, mucosal, and cell-mediated immune responses in vivo. More importantly, these specific immune responses could protect against subsequent wild-type HAdV-3 (BJ809) or HAdV-7 (BJ1026) challenge, showing a significant reduction in viral load and a noticeable alleviation of histopathological changes in the challenged mouse lung in a dose-dependent manner. These findings highlighted that recombinant rFLU/HAdV warrants further investigation as a promising HAdV candidate vaccine and underscored that the immuno-protection should be confirmed in primate models.

Keywords: HAdV; Hexon protein epitopes; Influenza virus; Viral vector.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae Infections / pathology
  • Adenoviridae Infections / prevention & control*
  • Adenoviruses, Human / genetics
  • Adenoviruses, Human / immunology*
  • Administration, Intranasal
  • Animals
  • Antibodies, Viral / blood
  • Capsid Proteins / genetics
  • Capsid Proteins / immunology*
  • Disease Models, Animal
  • Drug Carriers*
  • Epitopes / genetics
  • Epitopes / immunology*
  • Female
  • Genetic Vectors
  • Histocytochemistry
  • Immunity, Mucosal
  • Leukocytes, Mononuclear / immunology
  • Lung / pathology
  • Lung / virology
  • Mice, Inbred BALB C
  • Orthomyxoviridae / genetics*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology
  • Reverse Genetics
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology
  • Viral Load
  • Viral Nonstructural Proteins / genetics
  • Viral Nonstructural Proteins / immunology
  • Viral Vaccines / administration & dosage
  • Viral Vaccines / genetics
  • Viral Vaccines / immunology*

Substances

  • Antibodies, Viral
  • Capsid Proteins
  • Drug Carriers
  • Epitopes
  • INS1 protein, influenza virus
  • Recombinant Proteins
  • Vaccines, Synthetic
  • Viral Nonstructural Proteins
  • Viral Vaccines
  • hexon capsid protein, Adenovirus