Nasal delivery of H5N1 avian influenza vaccine formulated with GenJet™ or in vivo-jetPEI® induces enhanced serological, cellular and protective immune responses

Drug Deliv. 2018 Nov;25(1):773-779. doi: 10.1080/10717544.2018.1450909.

Abstract

Avian influenza virus infection is a serious public health threat and preventive vaccination is the most cost-effective public health intervention strategy. Unfortunately, currently available unadjuvanted avian influenza vaccines are poorly immunogenic and alternative vaccine formulations and delivery strategies are in urgent need to reduce the high risk of avian influenza pandemics. Cationic polymers have been widely used as vectors for gene delivery in vitro and in vivo. In this study, we formulated H5N1 influenza vaccines with GenJet™ or in vivo-jetPEI®, and showed that these formulations significantly enhanced the immunogenicity of H5N1 vaccines and conferred protective immunity in a mouse model. Detailed analyses of adaptive immune responses revealed that both formulations induced mixed TH1/TH2 antigen-specific CD4 T-cell responses, antigen-specific cytotoxic CD8 T-cell and memory B-cell responses. Our findings suggest that cationic polymers merit future development as potential adjuvants for mucosal delivery of poorly immunogenic vaccines.

Keywords: Cationic polymers; H5N1 vaccine; adaptive immunity; influenza; mouse model; protective immunity.

Publication types

  • Comparative Study

MeSH terms

  • Adaptive Immunity / drug effects*
  • Administration, Intranasal
  • Animals
  • Antibodies, Viral / analysis
  • Antibodies, Viral / biosynthesis
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Drug Compounding
  • Drug Delivery Systems*
  • Female
  • Immunity, Cellular / drug effects*
  • Immunogenicity, Vaccine
  • Indicators and Reagents / chemistry
  • Indicators and Reagents / metabolism
  • Influenza A Virus, H5N1 Subtype / immunology*
  • Influenza Vaccines / administration & dosage*
  • Influenza Vaccines / genetics
  • Influenza Vaccines / metabolism
  • Influenza Vaccines / therapeutic use
  • Influenza in Birds / immunology*
  • Influenza in Birds / metabolism
  • Influenza in Birds / prevention & control
  • Influenza in Birds / virology
  • Mice, Inbred BALB C
  • Poultry
  • Survival Analysis
  • Vaccines, Synthetic / administration & dosage*
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / metabolism
  • Vaccines, Synthetic / therapeutic use
  • Weight Loss / drug effects

Substances

  • Antibodies, Viral
  • Indicators and Reagents
  • Influenza Vaccines
  • Vaccines, Synthetic