Immune responses of mice inoculated with recombinant Lactobacillus plantarum NC8 expressing the fusion gene HA2 and 3M2e of the influenza virus and protection against different subtypes of influenza virus

Virus Res. 2019 Apr 2:263:64-72. doi: 10.1016/j.virusres.2019.01.001. Epub 2019 Jan 3.

Abstract

To evaluate the efficiency of preventing pathogenic avian influenza by vaccination with recombinant Lactobacillus plantarum (L. plantarum) that expresses conserved antigens, the mucosal and systemic immune responses in animals vaccinated with recombinant L. plantarum NC8-409-1 (NC8-pSIP409-pgsA'-HA2) and NC8-409-2 (NC8-pSIP409-pgsA'-3M2e-HA2) were evaluated. Our results showed that recombinant L. plantarum NC8-409-1 and NC8-409-2 could substantially stimulate the specific IgA titer in the intestine and the specific IgG antibody titer in the serum. We also found that recombinant L. plantarum induced increases in the number of B220+ IgA+ cells in Peyer's patches (PPs), in lymphocyte proliferation and in the number of IFN-γ+ producing CD8+ T cells after immunization in mice. Most importantly, the mice that were vaccinated with recombinant L. plantarum NC8-409-2 and NC8-409-1 were to some extent protected against infection challenge with the H9N2 and H1N1 viruses. In particular, NC8-409-2 provided up to 80% protection against the H9N2 virus, and NC8-409-1 provided up to 60% protection. Lung tissue pathology was also reduced. Therefore, recombinant L. plantarum NC8-409-2 and NC8-409-1 may be candidate oral vaccines against bird flu.

Keywords: Immune response; Influenza virus; Lactobacillus plantarum; Oral immunization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral / analysis
  • Antibodies, Viral / blood
  • Blood / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Proliferation
  • Disease Models, Animal
  • Drug Carriers*
  • Hemagglutinins, Viral / genetics
  • Hemagglutinins, Viral / immunology*
  • Immunoglobulin A / analysis
  • Immunoglobulin G / blood
  • Influenza A Virus, H1N1 Subtype / immunology
  • Influenza A Virus, H9N2 Subtype / immunology
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / genetics
  • Influenza Vaccines / immunology*
  • Interferon-gamma / metabolism
  • Intestines / immunology
  • Lactobacillus plantarum / genetics*
  • Lung / pathology
  • Mice
  • Orthomyxoviridae Infections / prevention & control*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology*
  • Survival Analysis
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology
  • Viral Matrix Proteins / genetics
  • Viral Matrix Proteins / immunology*

Substances

  • Antibodies, Viral
  • Drug Carriers
  • Hemagglutinins, Viral
  • Immunoglobulin A
  • Immunoglobulin G
  • Influenza Vaccines
  • M2 protein, Influenza A virus
  • Recombinant Fusion Proteins
  • Vaccines, Synthetic
  • Viral Matrix Proteins
  • hemagglutinin HA-2 fusogenic peptide, Influenza virus
  • Interferon-gamma