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

Publication Type Academic Article
Authors Bu W, Joyce M, Nguyen H, Banh D, Aguilar F, Tariq Z, Yap M, Tsujimura Y, Gillespie R, Tsybovsky Y, Andrews S, Narpala S, McDermott A, Rossmann M, Yasutomi Y, Nabel G, Kanekiyo M, Cohen J
Journal Immunity
Volume 50
Issue 5
Pagination 1305-1316.e6
Date Published 04/09/2019
ISSN 1097-4180
Keywords Antibodies, Neutralizing, Antibodies, Viral, B-Lymphocytes, Epithelial Cells, Epstein-Barr Virus Infections, Herpesvirus 4, Human, Membrane Glycoproteins, Viral Envelope Proteins
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.
DOI 10.1016/j.immuni.2019.03.010
PubMed ID 30979688
PubMed Central ID PMC6660903
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