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

Bu W 1 , Joyce MG 2 , Nguyen H 1 , Banh DV 1 , Aguilar F 1 , Tariq Z 1 Show all authors , Yap ML 3 , Tsujimura Y 4 , Gillespie RA 5 , Tsybovsky Y 6 , Andrews SF 5 , Narpala SR 5 , McDermott AB 5 , Rossmann MG 7 , Yasutomi Y 4 , Nabel GJ 5 , Kanekiyo M 5 , Cohen JI 8

Affiliations 

  • 1 Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
  • 2 Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20817, USA
  • 3 Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA; Present address: Department of Biological Science, Faculty of Science, Universiti Tunku Abdul Rahman, 31900 Kampar, Perak, Malaysia
  • 4 Laboratory of Immunoregulation and Vaccine Research, Tsukuba Primate Research Center, National Institutes of Biomedical Innovation, Health and Nutrition, Tsukuba, Ibaraki 305-0843, Japan
  • 5 Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
  • 6 Electron Microscopy Laboratory, Advanced Research Technology Facility, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD 21702, USA
  • 7 Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA
  • 8 Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: jcohen@niaid.nih.gov
Immunity, 2019 05 21;50(5):1305-1316.e6.
PMID: 30979688 DOI: 10.1016/j.immuni.2019.03.010

Abstract

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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