Analysis of the immunogenicity and bioactivities of a split influenza A/H7N9 vaccine mixed with MF59 adjuvant in BALB/c mice

Vaccine. 2016 Apr 29;34(20):2362-70. doi: 10.1016/j.vaccine.2016.03.037. Epub 2016 Mar 21.

Abstract

The H7N9 influenza virus caused significant mortality and morbidity in humans during an outbreak in China in 2013. A recombinant H7N9 influenza seed with hemagglutinin (HA) and neuraminidase (NA) gene segments from A/Zhejiang/DTID-ZJU01/2013(H7N9) and six internal protein gene segments from A/Puerto Rico/8/34(H1N1; PR8) were generated using reverse genetics. We sought to determine the immunogenic, protective properties, and mechanisms of a split avian influenza A/H7N9 vaccine mixed with MF59 adjuvant in comparison to vaccines that included other adjuvant. BALB/c mice were vaccinated with two doses of different amounts and combinations of this novel A/ZJU01/PR8/2013 split vaccine with adjuvant. Mice were subsequently challenged with A/Zhejiang/DTID-ZJU01/2013(H7N9) by intranasal inoculation. We verified that MF59 enhanced the HI, MN, and IgG antibody titers to influenza antigens. Compared with alum, MF59 could more potentially induce humoral immune responses and Th2 cytokine production after virus infection, while both MF59 and alum can slightly increase NK cell activity. This split H7N9 influenza vaccine with MF59 adjuvant could effectively induce antibody production and protect mice from H7N9 virus challenge. We have selected this vaccine for manufacture and future clinical studies to protect humans from H7N9 virus infection.

Keywords: Cytokines; H7N9; Immunity; MF59; Split vaccine.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Alum Compounds / administration & dosage
  • Animals
  • Antibodies, Viral / blood
  • Cytokines / immunology
  • Dose-Response Relationship, Immunologic
  • Immunity, Cellular
  • Immunity, Humoral
  • Immunoglobulin G / blood
  • Influenza A Virus, H7N9 Subtype
  • Influenza Vaccines / immunology*
  • Killer Cells, Natural / immunology
  • Male
  • Mice, Inbred BALB C
  • Neutralization Tests
  • Orthomyxoviridae Infections / prevention & control*
  • Polysorbates / administration & dosage*
  • Squalene / administration & dosage*
  • Th2 Cells / immunology

Substances

  • Adjuvants, Immunologic
  • Alum Compounds
  • Antibodies, Viral
  • Cytokines
  • Immunoglobulin G
  • Influenza Vaccines
  • MF59 oil emulsion
  • Polysorbates
  • aluminum sulfate
  • Squalene