Immunization with Components of the Viral Fusion Apparatus Elicits Antibodies That Neutralize Epstein-Barr Virus in B Cells and Epithelial Cells

Immunity. 2019 May 21;50(5):1305-1316.e6. doi: 10.1016/j.immuni.2019.03.010. Epub 2019 Apr 9.


Epstein-Barr virus (EBV) causes infectious mononucleosis and is associated with epithelial-cell cancers and B cell lymphomas. An effective EBV vaccine is not available. We found that antibodies to the EBV glycoprotein gH/gL complex were the principal components in human plasma that neutralized infection of epithelial cells and that antibodies to gH/gL and gp42 contributed to B cell neutralization. Immunization of mice and nonhuman primates with nanoparticle vaccines that displayed components of the viral-fusion machinery EBV gH/gL or gH/gL/gp42 elicited antibodies that potently neutralized both epithelial-cell and B cell infection. Immune serum from nonhuman primates inhibited EBV-glycoprotein-mediated fusion of epithelial cells and B cells and targeted an epitope critical for virus-cell fusion. Therefore, unlike the leading EBV gp350 vaccine candidate, which only protects B cells from infection, these EBV nanoparticle vaccines elicit antibodies that inhibit the virus-fusion apparatus and provide cell-type-independent protection from virus infection.

Keywords: B cell lymphoma; Epstein-Barr virus; infectious mononucleosis; nanoparticle; vaccine; virus fusion.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Viral / immunology*
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / virology
  • CHO Cells
  • Cell Fusion
  • Cell Line, Tumor
  • Cricetulus
  • Epithelial Cells / immunology*
  • Epithelial Cells / virology
  • Epstein-Barr Virus Infections / immunology
  • Epstein-Barr Virus Infections / prevention & control*
  • Female
  • HEK293 Cells
  • HeLa Cells
  • Herpesvirus 4, Human / immunology*
  • Humans
  • Immune Sera / administration & dosage
  • Macaca fascicularis
  • Male
  • Membrane Glycoproteins / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Vaccines, Virus-Like Particle / immunology
  • Viral Envelope Proteins / immunology*
  • Viral Vaccines / immunology
  • Virus Attachment


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Immune Sera
  • Membrane Glycoproteins
  • Vaccines, Virus-Like Particle
  • Viral Envelope Proteins
  • Viral Vaccines