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- Title
A gH/gL-encoding replicon vaccine elicits neutralizing antibodies that protect humanized mice against EBV challenge.
- Authors
Edwards, Kristina R.; Malhi, Harman; Schmidt, Karina; Davis, Amelia R.; Homad, Leah J.; Warner, Nikole L.; Chhan, Crystal B.; Scharffenberger, Samuel C.; Gaffney, Karen; Hinkley, Troy; Potchen, Nicole B.; Wang, Jing Yang; Price, Jason; McElrath, M. Juliana; Olson, James; King, Neil P.; Lund, Jennifer M.; Moodie, Zoe; Erasmus, Jesse H.; McGuire, Andrew T.
- 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+ 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.
- Subjects
EPITHELIAL cells; B cells; MONONUCLEOSIS; IMMUNOGLOBULINS; VACCINES; VACCINE development; T cells
- Publication
NPJ Vaccines, 2024, Vol 9, Issue 1, p1
- ISSN
2059-0105
- Publication type
Article
- DOI
10.1038/s41541-024-00907-y