Journal Article

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

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

2020

Overview

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 (IC50 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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Animals / Antibodies / Antibodies, Monoclonal - immunology / Antibodies, Monoclonal - pharmacology / Antibodies, Neutralizing - immunology / Antibodies, Neutralizing - pharmacology / Antibodies, Viral - immunology / Antibodies, Viral - pharmacology / Antigens / Antiviral agents / Antiviral Agents - pharmacology / Antiviral drugs / B cells / Beef cattle / Biology and life sciences / Cell Line / Characterization / Chemical compounds / Chlorocebus aethiops / Clinical trials / Cloning / Composition / Coronaviridae / Coronavirus infections / Coronavirus Infections - drug therapy / Coronaviruses / Dipeptidyl Peptidase 4 - genetics / Disease control / Disease prevention / Disease transmission / Drug therapy / Flow cytometry / Genetic engineering / Health aspects / Humans / Ibalizumab / Identification and classification / Immunization / Immunization (passive) / Immunoglobulins / Infection / Infections / Infectious diseases / Laboratories / Leukocytes, Mononuclear - immunology / Lung diseases / Lymphocytes B / Medicine and Health Sciences / Mice / Mice, Inbred C57BL / Mice, Transgenic / Middle East respiratory syndrome / Middle East Respiratory Syndrome Coronavirus - immunology / Monoclonal antibodies / Mortality / Palivizumab / Peripheral blood mononuclear cells / Pharmaceutical research / Pharmacology / Proteins / R&D / Republic of Korea / Research & development / Research and Analysis Methods / Respiratory diseases / Spike Glycoprotein, Coronavirus - immunology / Spike protein / Transgenic mice / Vaccines / Vero Cells / Viral infections