Protective efficacy of Fc targeting conserved influenza virus M2e antigen expressed by Lactobacillus plantarum

Antiviral Res. 2017 Feb:138:9-21. doi: 10.1016/j.antiviral.2016.11.025. Epub 2016 Nov 29.

Abstract

The influenza A (H1N1) virus is a highly contagious acute respiratory disease affecting pigs and humans. This disease causes severe economic loss in many countries, and developing mucosal vaccines is an efficient strategy to control the influenza virus. The neonatal Fc receptor (FcRn) plays an important role in transferring IgG across polarized epithelial cells. In the present study, an oral vaccine was developed using Lactobacillus plantarum to deliver the internal influenza viral protein M2e fused to an IgG Fc fragment. Oral vaccination with recombinant L. plantarum expressing 3M2e-Fc elicited Peyer's patch (PP) DC activation, improved the number of gamma interferon (IFN-γ)-producing T cells and increased the frequency of CD8+IFN-γ+ cells in the mesenteric lymph nodes (MLNs). In addition, the recombinant L. plantarum can induce PP B220+IgA+ expression and enhance specific sIgA secretion and the shaping of growth centers (GCs) in PPs. Furthermore, the data demonstrated that immunization with recombinant L. plantarum expressing 3M2e-Fc markedly reduced the viral load in the lung and protected against H1N1 influenza virus and mouse-adapted H9N2 avian influenza virus (AIV) challenge in BALB/c mice. Collectively, the data also showed that this vaccine strategy provided effective protective immunity against infection with homologous and heterologous influenza viruses in a mouse model and may be useful for future influenza vaccine development.

Keywords: Influenza virus; Lactobacillus plantarum; M2e; Neonatal Fc receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Antibodies, Viral / blood
  • Antigens, Viral / genetics
  • Antigens, Viral / immunology
  • Cross Protection
  • Immunoglobulin Fc Fragments / genetics
  • Immunoglobulin Fc Fragments / immunology*
  • Immunoglobulin G / chemistry
  • Immunoglobulin gamma-Chains / genetics
  • Immunoglobulin gamma-Chains / immunology*
  • Influenza A Virus, H1N1 Subtype / chemistry
  • Influenza A Virus, H1N1 Subtype / immunology
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / immunology*
  • Lactobacillus plantarum / genetics*
  • Lung / virology
  • Mice
  • Mice, Inbred BALB C
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / prevention & control*
  • Orthomyxoviridae Infections / virology
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology
  • Viral Load
  • Viral Matrix Proteins / genetics*
  • Viral Matrix Proteins / immunology*

Substances

  • Antibodies, Viral
  • Antigens, Viral
  • Immunoglobulin Fc Fragments
  • Immunoglobulin G
  • Immunoglobulin gamma-Chains
  • Influenza Vaccines
  • M2 protein, Influenza A virus
  • Vaccines, Synthetic
  • Viral Matrix Proteins