A Pentavalent Epstein-Barr Virus-Like Particle Vaccine Elicits High Titers of Neutralizing Antibodies against Epstein-Barr Virus Infection in Immunized Rabbits.

Gabriela M Escalante,Esther Rodriguez,Anne K Barasa,Joslyn Foley,Peng Ye,Lorraine Z Mutsvunguma,David H Mulama,Javier Gordon Ogembo,Murali Muniraju

doi:10.3390/vaccines8020169

Abstract

Primary infection with Epstein-Barr virus (EBV) is associated with acute infectious mononucleosis, whereas persistent infection is associated with chronic diseases such as autoimmune diseases and various types of cancer. Indeed, approximately 2% of all new cancer cases occurring annually worldwide are EBV-associated. Currently, there is no licensed EBV prophylactic vaccine. Selection of appropriate viral protein subunits is critical for development of an effective vaccine. Although the major EBV surface glycoprotein gp350/220 (gp350) has been proposed as an important prophylactic vaccine target, attempts to develop a potent vaccine based on gp350 alone have shown limited success in the clinic. We provide data showing that five EBV glycoproteins (gp350, gB, gp42, gH, and gL) involved in viral entry and infection can successfully be incorporated on the surface of EBV-like particles (EBV-LPs). These EBV-LPs, when administered together with aluminum hydroxide and monophosphoryl lipid A as adjuvants to New Zealand white rabbits, elicited EBV glycoprotein-specific antibodies capable of neutralizing viral infection in vitro in both B cells and epithelial cells, better than soluble gp350 ectodomain. Our findings suggest that a pentavalent EBV-LP formulation might be an ideal candidate for development as a safe and immunogenic EBV vaccine.

Highlights

Epstein-Barr Virus (EBV), known as human herpesvirus (HHV) 4, is the causative agent of infectious mononucleosis and is associated with the development of several human malignancies, including gastric carcinoma, nasopharyngeal carcinoma, Hodgkin lymphoma, and Burkitt lymphoma, among other B cell lymphoproliferative malignancies [1,2]
The remaining vaccine candidates solely focused on the membrane glycoprotein gp350/220, which is the major target of Epstein-Barr virus (EBV)-neutralizing antibodies and the most abundant glycoprotein on the surface of both
To produce a pentavalent EBV-like particles (EBV-LPs) incorporating glycoproteins involved in viral entry of B cells and epithelial cells, we first generated Chinese hamster ovary (CHO) cells stably expressing gp350, gB, gp42, and gH/gL

Summary

Introduction

Epstein-Barr Virus (EBV), known as human herpesvirus (HHV) 4, is the causative agent of infectious mononucleosis and is associated with the development of several human malignancies, including gastric carcinoma, nasopharyngeal carcinoma, Hodgkin lymphoma, and Burkitt lymphoma, among other B cell lymphoproliferative malignancies [1,2]. Despite the global health burden that EBV poses, an effective EBV prophylactic vaccine remains elusive [7]. Several prophylactic vaccine candidates have been tested in the clinic over the past three decades [8]. EBNA-3A-specific T cell responses in a Phase I clinical trial [9]. Immunization with this vaccine resulted in reduced incidence of infectious mononucleosis but not reduction of infection. The remaining vaccine candidates solely focused on the membrane glycoprotein gp350/220 (gp350), which is the major target of EBV-neutralizing antibodies (nAbs) and the most abundant glycoprotein on the surface of both

Methods

Results

Discussion

Conclusion