Characterization of a human monoclonal antibody generated from a B-cell specific for a prefusion-stabilized spike protein of Middle East respiratory syndrome coronavirus

Choi, Jang-Hoon; Woo, Hye-Min; Lee, Tae-young; Lee, So-young; Shim, Sang-Mu; Park, Woo-Jung; Yang, Jeong-Sun; Kim, Joo Ae; Yun, Mi-Ran; Kim, Dae-Won; Kim, Sung Soon; Zhang, Yi; Shi, Wei; Wang, Lingshu; Graham, Barney S.; Mascola, John R.; Wang, Nanshuang; McLellan, Jason S.; Lee, Joo-Yeon; Lee, Hansaem

Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory infection and continues to infect humans, thereby contributing to a high mortality rate (34.3% in 2019). In the absence of an available licensed vaccine and antiviral agent, therapeutic human antibodies have been suggested as candidates for treatment. In this study, human monoclonal antibodies were isolated by sorting B cells from patient’s PBMC cells with prefusion stabilized spike (S) probes and a direct immunoglobulin cloning strategy. We identified six receptor-binding domain (RBD)-specific and five S1 (non-RBD)-specific antibodies, among which, only the RBD-specific antibodies showed high neutralizing potency (IC(50) 0.006–1.787 μg/ml) as well as high affinity to RBD. Notably, passive immunization using a highly potent antibody (KNIH90-F1) at a relatively low dose (2 mg/kg) completely protected transgenic mice expressing human DPP4 against MERS-CoV lethal challenge. These results suggested that human monoclonal antibodies isolated by using the rationally designed prefusion MERS-CoV S probe could be considered potential candidates for the development of therapeutic and/or prophylactic antiviral agents for MERS-CoV human infection.