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.
【초록키워드】 Treatment, antibodies, Vaccine, Antiviral, antibody, Prophylactic, MERS-CoV, immunization, B cell, Immunoglobulin, RBD, humans, Human monoclonal antibody, low dose, therapeutic, Neutralizing, antiviral agent, Middle East, severe respiratory infection, domain, high affinity, human infection, transgenic mice, candidate, respiratory syndrome coronavirus, high mortality rate, prefusion, probe, infect, FIVE, absence, suggested, cause, contributing to, expressing, RBD-specific antibody, human DPP4, PBMC cell, 【제목키워드】 Spike protein, Human monoclonal antibody, B-cell, characterization, respiratory syndrome coronavirus, East,