Title | Immunization with Components of the Viral Fusion Apparatus Elicits Antibodies That Neutralize Epstein-Barr Virus in B Cells and Epithelial Cells. |
Publication Type | Journal Article |
Year of Publication | 2019 |
Authors | Bu W, M Joyce G, Nguyen H, Banh DV, Aguilar F, Tariq Z, Yap MLan, Tsujimura Y, Gillespie RA, Tsybovsky Y, Andrews SF, Narpala SR, McDermott AB, Rossmann MG, Yasutomi Y, Nabel GJ, Kanekiyo M, Cohen JI |
Journal | Immunity |
Volume | 50 |
Issue | 5 |
Pagination | 1305-1316.e6 |
Date Published | 2019 05 21 |
ISSN | 1097-4180 |
Keywords | Animals, Antibodies, Neutralizing, Antibodies, Viral, B-Lymphocytes, Cell Fusion, Cell Line, Tumor, CHO Cells, Cricetulus, Epithelial Cells, Epstein-Barr Virus Infections, Female, HEK293 Cells, HeLa Cells, Herpesvirus 4, Human, Humans, Immune Sera, Macaca fascicularis, Male, Membrane Glycoproteins, Mice, Mice, Inbred BALB C, Vaccines, Virus-Like Particle, Viral Envelope Proteins, Viral Vaccines, Virus Attachment |
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 |
Alternate Journal | Immunity |
PubMed ID | 30979688 |
PubMed Central ID | PMC6660903 |
Grant List | HHSN261200800001C / RC / CCR NIH HHS / United States HHSN261200800001E / CA / NCI NIH HHS / United States ZIA AI000978-13 / / Intramural NIH HHS / United States |
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