Kristina R Edwards, Harman Malhi, Karina Schmidt, Amelia R Davis, Leah J Homad, Nikole L Warner, Crystal B Chhan, Samuel C Scharffenberger, Karen Gaffney, Troy Hinkley, Nicole B Potchen, Jing Yang Wang, Jason Price, M Juliana McElrath, James Olson, Neil P King, Jennifer M Lund, Zoe Moodie, Jesse H Erasmus, Andrew T McGuire
{"title":"gH/gL 编码的复制子疫苗可激发中和抗体,保护人源化小鼠免受 EBV 病毒挑战。","authors":"Kristina R Edwards, Harman Malhi, Karina Schmidt, Amelia R Davis, Leah J Homad, Nikole L Warner, Crystal B Chhan, Samuel C Scharffenberger, Karen Gaffney, Troy Hinkley, Nicole B Potchen, Jing Yang Wang, Jason Price, M Juliana McElrath, James Olson, Neil P King, Jennifer M Lund, Zoe Moodie, Jesse H Erasmus, Andrew T McGuire","doi":"10.1038/s41541-024-00907-y","DOIUrl":null,"url":null,"abstract":"<p><p>Epstein-Barr virus (EBV) is associated with several malignancies, neurodegenerative disorders and is the causative agent of infectious mononucleosis. A vaccine that prevents EBV-driven morbidity and mortality remains an unmet need. EBV is orally transmitted, infecting both B cells and epithelial cells. Several virally encoded proteins are involved in entry. The gH/gL glycoprotein complex is essential for infectivity irrespective of cell type, while gp42 is essential for infection of B cells. gp350 promotes viral attachment by binding to CD21 or CD35 and is the most abundant glycoprotein on the virion. gH/gL, gp42 and gp350, are known targets of neutralizing antibodies and therefore relevant immunogens for vaccine development. Here, we developed and optimized the delivery of several alphavirus-derived replicon RNA (repRNA) vaccine candidates encoding gH/gL, gH/gL/gp42 or gp350 delivered by a cationic nanocarrier termed LION™. The lead candidate, encoding full-length gH/gL, elicited high titers of neutralizing antibodies that persisted for at least 8 months and a vaccine-specific CD8<sup>+</sup> T cell response. Transfer of vaccine-elicited IgG protected humanized mice from EBV-driven tumor formation and death following high-dose viral challenge. These data demonstrate that LION/repRNA-gH/gL is an ideal candidate vaccine for preventing EBV infection and/or related malignancies in humans.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":6.9000,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11208421/pdf/","citationCount":"0","resultStr":"{\"title\":\"A gH/gL-encoding replicon vaccine elicits neutralizing antibodies that protect humanized mice against EBV challenge.\",\"authors\":\"Kristina R Edwards, Harman Malhi, Karina Schmidt, Amelia R Davis, Leah J Homad, Nikole L Warner, Crystal B Chhan, Samuel C Scharffenberger, Karen Gaffney, Troy Hinkley, Nicole B Potchen, Jing Yang Wang, Jason Price, M Juliana McElrath, James Olson, Neil P King, Jennifer M Lund, Zoe Moodie, Jesse H Erasmus, Andrew T McGuire\",\"doi\":\"10.1038/s41541-024-00907-y\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Epstein-Barr virus (EBV) is associated with several malignancies, neurodegenerative disorders and is the causative agent of infectious mononucleosis. 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A gH/gL-encoding replicon vaccine elicits neutralizing antibodies that protect humanized mice against EBV challenge.
Epstein-Barr virus (EBV) is associated with several malignancies, neurodegenerative disorders and is the causative agent of infectious mononucleosis. A vaccine that prevents EBV-driven morbidity and mortality remains an unmet need. EBV is orally transmitted, infecting both B cells and epithelial cells. Several virally encoded proteins are involved in entry. The gH/gL glycoprotein complex is essential for infectivity irrespective of cell type, while gp42 is essential for infection of B cells. gp350 promotes viral attachment by binding to CD21 or CD35 and is the most abundant glycoprotein on the virion. gH/gL, gp42 and gp350, are known targets of neutralizing antibodies and therefore relevant immunogens for vaccine development. Here, we developed and optimized the delivery of several alphavirus-derived replicon RNA (repRNA) vaccine candidates encoding gH/gL, gH/gL/gp42 or gp350 delivered by a cationic nanocarrier termed LION™. The lead candidate, encoding full-length gH/gL, elicited high titers of neutralizing antibodies that persisted for at least 8 months and a vaccine-specific CD8+ T cell response. Transfer of vaccine-elicited IgG protected humanized mice from EBV-driven tumor formation and death following high-dose viral challenge. These data demonstrate that LION/repRNA-gH/gL is an ideal candidate vaccine for preventing EBV infection and/or related malignancies in humans.
NPJ VaccinesImmunology and Microbiology-Immunology
CiteScore
11.90
自引率
4.30%
发文量
146
审稿时长
11 weeks
期刊介绍:
Online-only and open access, npj Vaccines is dedicated to highlighting the most important scientific advances in vaccine research and development.