Poster - #UCLA-30 - Keywords: Epstein-Barr EBV vaccine cancer glycoprotein

A multivalent vaccine to elicit potent humoral immune responses to Epstein-Barr virus infection and its associated cancers

Gabriela M. Escalante'*, Murali Muniraju*, Lorraine Mutsvunguma*, Esther Rodriguez', Cloe Zimmerman'*, Javier Gordon Ogembo*
'Irell and Manella Graduate School, Beckman Research Institute of City of Hope, Duarte, CA, USA. *Department of Immuno-Oncology, Beckman Research Institute of City of Hope, Duarte, CA, USA

ABSTRACT:
Primary infection with Epstein-Barr virus (EBV) is associated with acute infectious mononucleosis, while persistent infection is associated with chronic diseases such as autoimmunity and various types of cancers. Indeed, ~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 an effective vaccine. Although the major EBV surface glycoprotein gp350/220 (gp350) has been proposed as a potentially important prophylactic vaccine target, attempts to develop a potent vaccine based on this target alone have shown limited success. In our laboratory, we have adopted the Modified Vaccinia Ankara (MVA) viral vector as a delivery platform for five EBV glycoproteins (gp350, gB, gp42, gL and gH) involved in virus entry and infection of diverse cell types permissive to EBV. We have constructed a recombinant MVA vector incorporating these five glycoproteins, and we show evidence that the vector robustly expresses each glycoprotein and that its genetic and transcriptional stability is maintained up to 10 viral passages. Importantly, we further show evidence that the vector is highly immunogenic in immunized BALB/c mice, resulting in high titers of glycoprotein-specific antibodies. Future studies will focus on testing the efficacy of vaccine-induced antibodies in a humanized mouse model of EBV challenge and testing immunogenicity in non-human primates, in preparation for clinical translation.