Escalante Gabriela M, Foley Joslyn, Mutsvunguma Lorraine Z, Rodriguez Esther, Mulama David H, Muniraju Murali, Ye Peng, Barasa Anne K, Ogembo Javier Gordon
Department of Immuno-Oncology, Irell & Manella Graduate School of Biological Sciences of City of Hope, Duarte, CA 91010, USA.
Department of Immuno-Oncology, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA.
Vaccines (Basel). 2020 Apr 6;8(2):169. doi: 10.3390/vaccines8020169.
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 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.
爱泼斯坦-巴尔病毒（EBV）的初次感染与急性传染性单核细胞增多症相关，而持续性感染则与自身免疫性疾病和各种类型癌症等慢性疾病相关。事实上，全球每年新发生的癌症病例中约有2%与EBV有关。目前，尚无获得许可的EBV预防性疫苗。选择合适的病毒蛋白亚基对于开发有效的疫苗至关重要。尽管主要的EBV表面糖蛋白gp350/220（gp350）已被提议作为重要的预防性疫苗靶点，但仅基于gp350开发有效疫苗的尝试在临床上显示出有限的成功。我们提供的数据表明，参与病毒进入和感染的五种EBV糖蛋白（gp350、gB、gp42、gH和gL）能够成功整合到类EBV颗粒（EBV-LPs）的表面。当将这些EBV-LPs与氢氧化铝和单磷酰脂质A作为佐剂一起给予新西兰白兔时，能诱导产生EBV糖蛋白特异性抗体，该抗体能够在B细胞和上皮细胞中中和病毒感染，效果优于可溶性gp350胞外域。我们的研究结果表明，五价EBV-LP制剂可能是开发安全且具有免疫原性的EBV疫苗的理想候选物。
