期刊
VACCINES
卷 9, 期 3, 页码 -出版社
MDPI
DOI: 10.3390/vaccines9030285
关键词
Epstein-Barr virus; infectious mononucleosis; EBV-associated lymphoma and epithelial cancer; EBV vaccine development; core fusion machinery; envelope glycoprotein; gH/gL; gB; neutralizing antibody
资金
- Dean's Research and Education Endowment Fund from Uniformed Services University of the Health Sciences (USUHS)
EBV core fusion machinery proteins can induce high titer EBV neutralizing antibodies for both B lymphocytes and epithelial cells, with a synergistic effect when gH/gL is combined with trimeric gB. The sera from immunized rabbits not only protect humanized mice from lethal EBV challenge, but also significantly reduce EBV load in peripheral blood. These findings suggest that the combination of gH/gL and trimeric gB could be a promising prophylactic EBV vaccine.
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.
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