Immunization with Epstein–Barr Virus Core Fusion Machinery Envelope Proteins Elicit High Titers of Neutralizing Activities and Protect Humanized Mice from Lethal Dose EBV Challenge

Epstein–Barr virus (EBV) is the primary cause of infectious mononucleosis and is strongly implicated in the etiology of multiple lymphoid and epithelial cancers. EBV core fusion machinery envelope proteins gH/gL and gB coordinately mediate EBV fusion and entry into its target cells, B lymphocytes an...

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Main Authors: Xinle Cui, Zhouhong Cao, Yuriko Ishikawa, Sara Cui, Ken-Ichi Imadome, Clifford M. Snapper
Format: Article
Language:English
Published: MDPI AG 2021-03-01
Series:Vaccines
Subjects:
Online Access:https://www.mdpi.com/2076-393X/9/3/285
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spelling doaj-566d4e2fd68b4425a9265cc487fd24482021-03-20T00:04:44ZengMDPI AGVaccines2076-393X2021-03-01928528510.3390/vaccines9030285Immunization with Epstein–Barr Virus Core Fusion Machinery Envelope Proteins Elicit High Titers of Neutralizing Activities and Protect Humanized Mice from Lethal Dose EBV ChallengeXinle Cui0Zhouhong Cao1Yuriko Ishikawa2Sara Cui3Ken-Ichi Imadome4Clifford M. Snapper5The Institute for Vaccine Research, Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USAThe Institute for Vaccine Research, Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USADepartment of Advanced Medicine for Infections, National Center for Child Health and Development, Tokyo 157-0074, JapanThe Institute for Vaccine Research, Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USADepartment of Advanced Medicine for Infections, National Center for Child Health and Development, Tokyo 157-0074, JapanDepartment of Advanced Medicine for Infections, National Center for Child Health and Development, Tokyo 157-0074, JapanEpstein–Barr virus (EBV) is the primary cause of infectious mononucleosis and is strongly implicated in the etiology of multiple lymphoid and epithelial cancers. EBV core fusion machinery envelope proteins gH/gL and gB coordinately mediate EBV fusion and entry into its target cells, B lymphocytes and epithelial cells, suggesting these proteins could induce antibodies that prevent EBV infection. We previously reported that the immunization of rabbits with recombinant EBV gH/gL or trimeric gB each induced markedly higher serum EBV-neutralizing titers for B lymphocytes than that of the leading EBV vaccine candidate gp350. In this study, we demonstrated that immunization of rabbits with EBV core fusion machinery proteins induced high titer EBV neutralizing antibodies for both B lymphocytes and epithelial cells, and EBV gH/gL in combination with EBV trimeric gB elicited strong synergistic EBV neutralizing activities. Furthermore, the immune sera from rabbits immunized with EBV gH/gL or trimeric gB demonstrated strong passive immune protection of humanized mice from lethal dose EBV challenge, partially or completely prevented death respectively, and markedly decreased the EBV load in peripheral blood of humanized mice. These data strongly suggest the combination of EBV core fusion machinery envelope proteins gH/gL and trimeric gB is a promising EBV prophylactic vaccine.https://www.mdpi.com/2076-393X/9/3/285Epstein–Barr virusinfectious mononucleosisEBV-associated lymphoma and epithelial cancerEBV vaccine developmentcore fusion machineryenvelope glycoprotein
collection DOAJ
language English
format Article
sources DOAJ
author Xinle Cui
Zhouhong Cao
Yuriko Ishikawa
Sara Cui
Ken-Ichi Imadome
Clifford M. Snapper
spellingShingle Xinle Cui
Zhouhong Cao
Yuriko Ishikawa
Sara Cui
Ken-Ichi Imadome
Clifford M. Snapper
Immunization with Epstein–Barr Virus Core Fusion Machinery Envelope Proteins Elicit High Titers of Neutralizing Activities and Protect Humanized Mice from Lethal Dose EBV Challenge
Vaccines
Epstein–Barr virus
infectious mononucleosis
EBV-associated lymphoma and epithelial cancer
EBV vaccine development
core fusion machinery
envelope glycoprotein
author_facet Xinle Cui
Zhouhong Cao
Yuriko Ishikawa
Sara Cui
Ken-Ichi Imadome
Clifford M. Snapper
author_sort Xinle Cui
title Immunization with Epstein–Barr Virus Core Fusion Machinery Envelope Proteins Elicit High Titers of Neutralizing Activities and Protect Humanized Mice from Lethal Dose EBV Challenge
title_short Immunization with Epstein–Barr Virus Core Fusion Machinery Envelope Proteins Elicit High Titers of Neutralizing Activities and Protect Humanized Mice from Lethal Dose EBV Challenge
title_full Immunization with Epstein–Barr Virus Core Fusion Machinery Envelope Proteins Elicit High Titers of Neutralizing Activities and Protect Humanized Mice from Lethal Dose EBV Challenge
title_fullStr Immunization with Epstein–Barr Virus Core Fusion Machinery Envelope Proteins Elicit High Titers of Neutralizing Activities and Protect Humanized Mice from Lethal Dose EBV Challenge
title_full_unstemmed Immunization with Epstein–Barr Virus Core Fusion Machinery Envelope Proteins Elicit High Titers of Neutralizing Activities and Protect Humanized Mice from Lethal Dose EBV Challenge
title_sort immunization with epstein–barr virus core fusion machinery envelope proteins elicit high titers of neutralizing activities and protect humanized mice from lethal dose ebv challenge
publisher MDPI AG
series Vaccines
issn 2076-393X
publishDate 2021-03-01
description Epstein–Barr virus (EBV) is the primary cause of infectious mononucleosis and is strongly implicated in the etiology of multiple lymphoid and epithelial cancers. EBV core fusion machinery envelope proteins gH/gL and gB coordinately mediate EBV fusion and entry into its target cells, B lymphocytes and epithelial cells, suggesting these proteins could induce antibodies that prevent EBV infection. We previously reported that the immunization of rabbits with recombinant EBV gH/gL or trimeric gB each induced markedly higher serum EBV-neutralizing titers for B lymphocytes than that of the leading EBV vaccine candidate gp350. In this study, we demonstrated that immunization of rabbits with EBV core fusion machinery proteins induced high titer EBV neutralizing antibodies for both B lymphocytes and epithelial cells, and EBV gH/gL in combination with EBV trimeric gB elicited strong synergistic EBV neutralizing activities. Furthermore, the immune sera from rabbits immunized with EBV gH/gL or trimeric gB demonstrated strong passive immune protection of humanized mice from lethal dose EBV challenge, partially or completely prevented death respectively, and markedly decreased the EBV load in peripheral blood of humanized mice. These data strongly suggest the combination of EBV core fusion machinery envelope proteins gH/gL and trimeric gB is a promising EBV prophylactic vaccine.
topic Epstein–Barr virus
infectious mononucleosis
EBV-associated lymphoma and epithelial cancer
EBV vaccine development
core fusion machinery
envelope glycoprotein
url https://www.mdpi.com/2076-393X/9/3/285
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