Antigenicity and immunogenicity of HA2 and M2e influenza virus antigens conjugated to norovirus-like, VP1 capsid-based particles by the SpyTag/SpyCatcher technology

Virology. 2022 Jan:566:89-97. doi: 10.1016/j.virol.2021.12.001. Epub 2021 Dec 3.

Abstract

Virus-like particles (VLPs) modified through different molecular technologies are employed as delivery vehicles or platforms for heterologous antigen display. We have recently created a norovirus (NoV) VLP platform, where two influenza antigens, the extracellular domain of matrix protein M2 (M2e) or the stem domain of the major envelope glycoprotein hemagglutinin (HA2) are displayed on the surface of the NoV VLPs by SpyTag/SpyCatcher conjugation. To demonstrate the feasibility of the platform to deliver foreign antigens, this study examined potential interference of the conjugation with induction of antibodies against conjugated M2e peptide, HA2, and NoV VLP carrier. High antibody response was induced by HA2 but not M2e decorated VLPs. Furthermore, HA2-elicited antibodies did not neutralize the homologous influenza virus in vitro. Conjugated NoV VLPs retained intact receptor binding capacity and self-immunogenicity. The results demonstrate that NoV VLPs could be simultaneously used as a platform to deliver foreign antigens and a NoV vaccine.

Keywords: HA2; Influenza virus; M2e; Norovirus; Platform; SpyTag/SpyCatcher; VLP; Vaccine; Virus-like particle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral / biosynthesis*
  • Antigens, Viral / genetics
  • Antigens, Viral / immunology
  • Capsid Proteins / genetics
  • Capsid Proteins / immunology
  • Female
  • Hemagglutinins, Viral / genetics*
  • Hemagglutinins, Viral / immunology
  • Humans
  • Immunoconjugates / genetics
  • Immunoconjugates / immunology
  • Immunogenicity, Vaccine
  • Immunoglobulin G / biosynthesis*
  • Influenza A Virus, H1N1 Subtype / immunology
  • Influenza A Virus, H1N1 Subtype / pathogenicity
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / biosynthesis
  • Influenza Vaccines / genetics*
  • Influenza, Human / immunology
  • Influenza, Human / prevention & control*
  • Influenza, Human / virology
  • Mice
  • Mice, Inbred BALB C
  • Norovirus / genetics
  • Norovirus / immunology
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / prevention & control*
  • Orthomyxoviridae Infections / virology
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Vaccination / methods
  • Vaccines, Virus-Like Particle / administration & dosage
  • Vaccines, Virus-Like Particle / biosynthesis
  • Vaccines, Virus-Like Particle / genetics*
  • Viral Matrix Proteins / genetics
  • Viral Matrix Proteins / immunology

Substances

  • Antibodies, Viral
  • Antigens, Viral
  • Capsid Proteins
  • Hemagglutinins, Viral
  • Immunoconjugates
  • Immunoglobulin G
  • Influenza Vaccines
  • M1 protein, Influenza A virus
  • Recombinant Fusion Proteins
  • Vaccines, Virus-Like Particle
  • Viral Matrix Proteins
  • hemagglutinin HA-2 fusogenic peptide, Influenza virus