Marburg virus-like particles produced in insect cells induce neutralizing antibodies in rhesus macaques

J Med Virol. 2017 Dec;89(12):2069-2074. doi: 10.1002/jmv.24832. Epub 2017 Sep 1.

Abstract

Marburg virus (MARV), which is one of the most virulent agents in the world, causes lethal haemorrhagic fever in humans and nonhuman primates (NHPs) with a mortality rate of up to 90%. Currently, there is no effective treatment or approved vaccine for MARV for human use to control disease outbreak and spread. Virus-like particles (VLPs), which are morphologically identical to the native infectious virus particle, are efficacious as vaccines against many viruses, including human papilloma virus (HPV), porcine circovirus (PCV) type 2 and hepatitis B virus (HBV). In this study, we generated MARV virus-like particles (VLPs) by co-expressing a glycoprotein (GP) and matrix protein (VP40) using the baculovirus expression system. Rhesus macaques vaccinated with MARV VLPs mixed with adjuvant Poria cocos polysaccharides (PCP-II) produced a GP-specific IgG titer of up to 1:1280 and virus-neutralizing antibody titers that reached 1:320. MARV VLPs also elicited interferon-γ (IFN-γ) and interleukin-4 (IL-4) secretion associated with T-helper 1 cell (Th1)- and T-helper 2 cell (Th2)-mediated immunity, as detected using enzyme-linked immunospot (ELISpot) assays. These data indicate that MARV VLPs mixed with adjuvant PCP-II have excellent immunogenicity in rhesus macaques and may be a promising candidate vaccine against MARV.

Keywords: Marburg virus; VLPs; immune response; nonhuman primates; vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / biosynthesis
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Viral / biosynthesis
  • Antibodies, Viral / immunology*
  • Enzyme-Linked Immunospot Assay
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-4 / metabolism
  • Macaca mulatta
  • Marburg Virus Disease / immunology
  • Marburg Virus Disease / virology
  • Marburgvirus / genetics
  • Marburgvirus / immunology*
  • Marburgvirus / isolation & purification
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology
  • Sf9 Cells
  • Vaccines, Virus-Like Particle / biosynthesis
  • Vaccines, Virus-Like Particle / immunology*
  • Viral Matrix Proteins / genetics
  • Viral Matrix Proteins / immunology
  • Viral Vaccines / immunology*

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Membrane Glycoproteins
  • VP40 protein, virus
  • Vaccines, Virus-Like Particle
  • Viral Matrix Proteins
  • Viral Vaccines
  • Interleukin-4
  • Interferon-gamma