Center for Immunity and Immunotherapies and Program for Cell and Gene Therapy, Seattle Children's Research Institute, Seattle, WA98101, USA.
These authors contributed equally.
Cell Rep Med. 2020 Jun 23;1(3). doi: 10.1016/j.xcrm.2020.100033.
Epstein-Barr virus (EBV) is a cancer-associated pathogen for which there is no vaccine. Successful anti-viral vaccines elicit antibodies that neutralize infectivity; however, it is unknown whether neutralizing antibodies prevent EBV acquisition. Here we assessed whether passively delivered AMMO1, a monoclonal antibody that neutralizes EBV in a cell-type-independent manner, could protect against experimental EBV challenge in two animal infection models. When present prior to a high-dose intravenous EBV challenge, AMMO1 prevented viremia and reduced viral loads to nearly undetectable levels in humanized mice. AMMO1 conferred sterilizing immunity to three of four macaques challenged orally with rhesus lymphocryptovirus, the EBV ortholog that infects rhesus macaques. The infected macaque had lower plasma neutralizing activity than the protected animals. These results indicate that a vaccine capable of eliciting adequate titers of neutralizing antibodies targeting the AMMO1 epitope may protect against EBV acquisition and are therefore highly relevant to the design of an effective EBV vaccine.
EB 病毒(EBV)是一种与癌症相关的病原体,目前尚无针对该病毒的疫苗。成功的抗病毒疫苗会引发中和感染力的抗体;然而,目前尚不清楚中和抗体是否能预防 EBV 的感染。在这里,我们评估了被动给予 AMMO1(一种以细胞类型非依赖性方式中和 EBV 的单克隆抗体)是否能在两种动物感染模型中预防实验性 EBV 挑战。当在高剂量静脉内 EBV 挑战之前存在时,AMMO1 可预防人源化小鼠的病毒血症,并将病毒载量降低至几乎无法检测的水平。AMMO1 对用恒河猴淋巴组织细胞病毒(感染恒河猴的 EBV 同源物)经口挑战的四只猕猴中的三只赋予了绝育免疫力。感染的猕猴的血浆中和活性低于受保护的动物。这些结果表明,一种能够引发针对 AMMO1 表位的足够中和抗体滴度的疫苗,可能预防 EBV 的感染,因此与 EBV 有效疫苗的设计高度相关。