Production of Multi-Subtype Influenza Virus-Like Particles by Molecular Fusion with BAFF or APRIL for Vaccine Development

Methods Mol Biol. 2021:2248:139-153. doi: 10.1007/978-1-0716-1130-2_10.

Abstract

Virus-like particle (VLP) technology is an alternative platform for developing vaccines to combat seasonal and pandemic influenza. Influenza VLPs are non-infectious nanoparticles that can elicit effective vaccine immunogenicity in hosts. B-cell-activating factor (BAFF, or BLyS) and a proliferation-inducing ligand (APRIL) are members of the tumor necrosis factor (TNF) superfamily of cytokines. Both BAFF and APRIL are homotrimers that interact with homotrimeric receptors. Here, we report a method of the production of influenza VLPs by molecular incorporation with BAFF or APRIL homotrimers to interact with their receptors. We engineered the VLPs by direct fusion of BAFF or APRIL to the transmembrane anchored domain of the hemagglutinin (HA) gene. We also describe procedures for the production of BAFF-VLPs containing H5H7 and H1H5H7 for multi-subtype vaccine development.

Keywords: APRIL; BAFF; Influenza VLP; Molecular fusion; Multi-subtype vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Viral / genetics
  • Antigens, Viral / immunology*
  • B-Cell Activating Factor / genetics
  • B-Cell Activating Factor / immunology*
  • Baculoviridae / genetics
  • Cloning, Molecular
  • Gene Expression
  • Hemagglutination Tests
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology
  • Humans
  • Influenza A Virus, H5N1 Subtype / immunology
  • Influenza Vaccines / immunology*
  • Plasmids / genetics
  • Recombinant Fusion Proteins* / immunology
  • Tumor Necrosis Factor Ligand Superfamily Member 13 / genetics
  • Tumor Necrosis Factor Ligand Superfamily Member 13 / immunology*
  • Vaccines, Virus-Like Particle / immunology*

Substances

  • Antigens, Viral
  • B-Cell Activating Factor
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Influenza Vaccines
  • Recombinant Fusion Proteins
  • TNFSF13 protein, human
  • TNFSF13B protein, human
  • Tumor Necrosis Factor Ligand Superfamily Member 13
  • Vaccines, Virus-Like Particle