Coadministration of Recombinant Adenovirus Expressing GM-CSF with Inactivated H5N1 Avian Influenza Vaccine Increased the Immune Responses and Protective Efficacy Against a Wild Bird Source of H5N1 Challenge

J Interferon Cytokine Res. 2017 Oct;37(10):467-473. doi: 10.1089/jir.2017.0043.

Abstract

Wild birds play a key role in the spread of avian influenza virus (AIV). There is a continual urgent requirement for AIV vaccines to address the ongoing genetic changes of AIV. In the current study, we trialed a novel AIV vaccine against the wild bird source of H5N1 type AIV with recombinant adenovirus expressing granulocyte monocyte colony-stimulating factor (GM-CSF) as an adjuvant. A total of 150-day-old commercial chicks, with AIV-maternal-derived antibody, were divided into 6 groups. The primary vaccination was performed at day 14 followed by a subsequent boosting and intramuscular challenge on day 28 and 42, respectively. Recombinant GM-CSF (rGM-CSF) expressed by adenovirus, named as rAd-GM-CSF, raised the hemagglutination inhibition (HI) titers (log2) against AIV from 7.0 (vaccinate with inactivated vaccine alone) to 8.4 after booster immunization. Moreover, the rGM-CSF addition markedly increased the expression of interferon-γ, interleukin-4, and major histocompatibility complex-II in the lungs, compared with those immunized with inactivated vaccine alone on day 29, that is, 18 h post booster immunization. Following challenge, chicks inoculated with the inactivated AIV vaccine and rAd-GM-CSF together exhibited mild clinical signs and 62% survivals compared to 33% in the group immunized with inactivated AIV vaccine alone. Higher level of HI titers, immune related molecule expressions, and protection ratio demonstrates a good potential of rGM-CSF in improving humoral and cell mediated immune responses of inactivated AIV vaccines.

Keywords: GM-CSF; H5N1; adjuvant; vaccine; wild bird.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Animals
  • Antibodies, Viral / immunology
  • Chickens
  • Genetic Vectors / administration & dosage*
  • Genetic Vectors / genetics*
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics*
  • Humans
  • Immunity, Humoral
  • Immunization, Secondary
  • Influenza A Virus, H5N1 Subtype / genetics
  • Influenza A Virus, H5N1 Subtype / immunology*
  • Influenza Vaccines / administration & dosage*
  • Influenza Vaccines / immunology
  • Influenza in Birds / immunology
  • Influenza in Birds / mortality
  • Influenza in Birds / virology
  • Influenza, Human / immunology*
  • Influenza, Human / prevention & control*
  • Influenza, Human / virology
  • Lung / immunology
  • Lung / metabolism
  • Lung / pathology
  • Lung / virology
  • Lymphocyte Activation / immunology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Vaccination
  • Virus Shedding

Substances

  • Antibodies, Viral
  • Influenza Vaccines
  • Granulocyte-Macrophage Colony-Stimulating Factor