Back to Search
Start Over
A gH/gL-encoding replicon vaccine elicits neutralizing antibodies that protect humanized mice against EBV challenge.
- Source :
-
NPJ vaccines [NPJ Vaccines] 2024 Jun 26; Vol. 9 (1), pp. 120. Date of Electronic Publication: 2024 Jun 26. - Publication Year :
- 2024
-
Abstract
- 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 <superscript>+</superscript> 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.<br /> (© 2024. The Author(s).)
Details
- Language :
- English
- ISSN :
- 2059-0105
- Volume :
- 9
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- NPJ vaccines
- Publication Type :
- Academic Journal
- Accession number :
- 38926438
- Full Text :
- https://doi.org/10.1038/s41541-024-00907-y