Cui Xinle, Cao Zhouhong, Ishikawa Yuriko, Cui Sara, Imadome Ken-Ichi, Snapper Clifford M
The Institute for Vaccine Research, Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Vaccines (Basel). 2021 Mar 19;9(3):285. doi: 10.3390/vaccines9030285.
Epstein-Barr virus (EBV) is the primary cause of infectious mononucleosis and is strongly implicated in the etiology of multiple lymphoid and epithelial cancers. EBV core fusion machinery envelope proteins gH/gL and gB coordinately mediate EBV fusion and entry into its target cells, B lymphocytes and epithelial cells, suggesting these proteins could induce antibodies that prevent EBV infection. We previously reported that the immunization of rabbits with recombinant EBV gH/gL or trimeric gB each induced markedly higher serum EBV-neutralizing titers for B lymphocytes than that of the leading EBV vaccine candidate gp350. In this study, we demonstrated that immunization of rabbits with EBV core fusion machinery proteins induced high titer EBV neutralizing antibodies for both B lymphocytes and epithelial cells, and EBV gH/gL in combination with EBV trimeric gB elicited strong synergistic EBV neutralizing activities. Furthermore, the immune sera from rabbits immunized with EBV gH/gL or trimeric gB demonstrated strong passive immune protection of humanized mice from lethal dose EBV challenge, partially or completely prevented death respectively, and markedly decreased the EBV load in peripheral blood of humanized mice. These data strongly suggest the combination of EBV core fusion machinery envelope proteins gH/gL and trimeric gB is a promising EBV prophylactic vaccine.
爱泼斯坦-巴尔病毒（EBV）是传染性单核细胞增多症的主要病因，并且与多种淋巴和上皮癌的病因密切相关。EBV核心融合机制包膜蛋白gH/gL和gB协同介导EBV融合并进入其靶细胞，即B淋巴细胞和上皮细胞，这表明这些蛋白可能诱导产生预防EBV感染的抗体。我们之前报道，用重组EBV gH/gL或三聚体gB免疫兔子，相较于主要的EBV疫苗候选物gp350，每种都能诱导出显著更高的针对B淋巴细胞的血清EBV中和滴度。在本研究中，我们证明用EBV核心融合机制蛋白免疫兔子可诱导出针对B淋巴细胞和上皮细胞的高滴度EBV中和抗体，并且EBV gH/gL与EBV三聚体gB联合使用可引发强大的协同EBV中和活性。此外，用EBV gH/gL或三聚体gB免疫兔子所得的免疫血清对人源化小鼠具有强大的被动免疫保护作用，可使其免受致死剂量的EBV攻击，分别部分或完全防止死亡，并显著降低人源化小鼠外周血中的EBV载量。这些数据有力地表明，EBV核心融合机制包膜蛋白gH/gL和三聚体gB的组合是一种很有前景的EBV预防性疫苗。
