Epstein-Barr virus (EBV), an oncogenic gammaherpesvirus, causes acute
infectious mononucleosis (AIM) and is linked to the development of several human
malignancies. There is an urgent need for a
vaccine that is safe, prevents
infection and/or limits disease. Unique among human herpesviruses,
glycoprotein (gp)350/220, which initiates EBV attachment to susceptible host cells, is the major
ligand on the EBV envelope and is highly conserved. Interaction between gp350/220 and
complement receptor type 2 (CR2)/CD21 and/or (CR1)/CD35 on B-cells is required for
infection. Potent antibody responses to gp350/220 occur in animal models and humans. Thus, gp350/220 provides an attractive candidate for prophylactic
subunit vaccine development. However, in a recent Phase II clinical trial immunization with soluble recombinant gp350 reduced the incidence of AIM, but did not prevent
infection. Despite various attempts to produce an EBV
vaccine, no
vaccine is licensed. Herein we describe a sub-unit
vaccine against EBV based on a novel Newcastle disease virus (NDV)-virus-like particle (VLP) platform consisting of EBVgp350/220 ectodomain fused to NDV-fusion (F)
protein. The chimeric
protein EBVgp350/220-F is incorporated into the membrane of a VLP composed of the NDV matrix and
nucleoprotein. The particles resemble native EBV in diameter and shape and bind CD21 and CD35. Immunization of BALB/c mice with EBVgp350/220-F VLPs elicited strong, long-lasting
neutralizing antibody responses when assessed in vitro. This chimeric VLP is predicted to provide a superior safety profile as it is efficiently produced in Chinese hamster ovary (CHO) cells using a platform devoid of human
nucleic acid and EBV-transforming genes.