Department of Medicine, Infectious Diseases Division, Brigham and Women's Hospital and Department of Microbiology, Harvard Medical School, Boston, MA, USA.
Tulane National Primate Research Center, Covington, LA, USA.
Cell Rep Med. 2021 Jul 21;2(7):100352. doi: 10.1016/j.xcrm.2021.100352. eCollection 2021 Jul 20.
Epstein-Barr virus (EBV) and related lymphocryptoviruses (LCVs) from nonhuman primates are transmitted through oral secretions, penetrate the mucosal epithelium, and establish persistent infection in B cells. To determine whether neutralizing antibodies against epithelial or B cell infection could block oral transmission and persistent LCV infection, we use rhesus macaques, the most accurate animal model for EBV infection by faithfully reproducing acute and persistent infection in humans. Naive animals are infused with monoclonal antibodies neutralizing epithelial cell infection or B cell infection and then challenged orally with recombinant rhesus LCV. Our data show that high-titer B cell-neutralizing antibodies alone, but not epithelial cell-neutralizing antibodies, can provide complete protection of rhesus macaques from oral LCV challenge, but not in all hosts. Thus, neutralizing antibodies against B cell infection are important targets for EBV vaccine development, but they may not be sufficient.
EB 病毒(EBV)和相关的淋巴组织细胞病毒(LCVs)从非人类灵长类动物通过口腔分泌物传播,穿透黏膜上皮,并在 B 细胞中建立持续感染。为了确定针对上皮细胞或 B 细胞感染的中和抗体是否可以阻断口腔传播和持续的 LCV 感染,我们使用恒河猴作为最准确的 EBV 感染动物模型,因为它忠实地复制了人类的急性和持续性感染。未感染的动物被注入中和上皮细胞感染或 B 细胞感染的单克隆抗体,然后用重组恒河猴 LCV 进行口腔挑战。我们的数据表明,高滴度的 B 细胞中和抗体可以单独提供对恒河猴口腔 LCV 挑战的完全保护,但并非在所有宿主中都如此。因此,针对 B 细胞感染的中和抗体是 EBV 疫苗开发的重要靶点,但它们可能还不够。