Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, China.
State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Front Immunol. 2022 Jan 31;13:823949. doi: 10.3389/fimmu.2022.823949. eCollection 2022.
Middle East respiratory syndrome coronavirus (MERS-CoV) is an emergent coronavirus that has caused frequent zoonotic events through camel-to-human spillover. An effective camelid vaccination strategy is probably the best way to reduce human exposure risk. Here, we constructed and evaluated an inactivated rabies virus-vectored MERS-CoV vaccine in mice, camels, and alpacas. Potent antigen-specific antibody and CD8 T-cell responses were generated in mice; moreover, the vaccination reduced viral replication and accelerated virus clearance in MERS-CoV-infected mice. Besides, protective antibody responses against both MERS-CoV and rabies virus were induced in camels and alpacas. Satisfyingly, the immune sera showed broad cross-neutralizing activity against the three main MERS-CoV clades. For further characterization of the antibody response induced in camelids, MERS-CoV-specific variable domains of heavy-chain-only antibody (VHHs) were isolated from immunized alpacas and showed potent prophylactic and therapeutic efficacies in the Ad5-hDPP4-transduced mouse model. These results highlight the inactivated rabies virus-vectored MERS-CoV vaccine as a promising camelid candidate vaccine.
中东呼吸综合征冠状病毒（MERS-CoV）是一种新兴的冠状病毒，通过骆驼向人类溢出，频繁引发人畜共患病事件。一种有效的骆驼科动物疫苗接种策略可能是降低人类暴露风险的最佳途径。在这里，我们构建并评估了一种在小鼠、骆驼和羊驼中使用的灭活狂犬病病毒载体 MERS-CoV 疫苗。该疫苗在小鼠中产生了有效的抗原特异性抗体和 CD8 T 细胞应答；此外，该疫苗接种还降低了 MERS-CoV 感染小鼠中的病毒复制和加速了病毒清除。此外，骆驼和羊驼也产生了针对 MERS-CoV 和狂犬病病毒的保护性抗体应答。令人满意的是，免疫血清显示出对三种主要 MERS-CoV 分支的广泛交叉中和活性。为了进一步表征骆驼科动物中诱导的抗体应答，从免疫的羊驼中分离出了 MERS-CoV 特异性重链单域抗体（VHHs），并在 Ad5-hDPP4 转导的小鼠模型中显示出强大的预防和治疗效果。这些结果突出了灭活狂犬病病毒载体 MERS-CoV 疫苗作为一种有前途的骆驼科候选疫苗。
