Discovery of Potent Therapeutic Human Monoclonal Antibody Candidates against MERS coronavirus
Hye-Min Woo1, Hyemin Ko1, Sang-Mu Shim1, Joo-Yeon Lee1, Hansaem Lee1*
1Division of Emerging Infectious Disease & Vector Research, Center for Infectious Diseases Research, National Institute of Health, Korea CDC, Cheongju-si, South Korea
*Corresponding Author: Hansaem Lee, E-mail: email@example.com
Since 2012, the outbreaks of Middle East respiratory syndrome (MERS) have occurred in 27 countries, 2,207 laboratory-confirmed cases of MERS-CoV infection were notified, and 787 deaths occurred. Although high mortality (~35%) by MERS infection has been reported, there is currently no specific vaccine or treatment for MERS-CoV.
Human monoclonal neutralizing antibodies has been developed for therapeutic or prophylactic use against newly emerging infectious diseases including MERS. Antibodies neutralize viral infection by interfering with virions that bind to receptors, blocking virus entry into cells and virus propagation.
In this study, we presented seven human monoclonal antibodies (mAbs) isolated from peripheral blood mononuclear cells of convalescent Korean MERS patients, specifically binding to MERS-CoV spike protein S1. Out of 7 candidates, three antibodies were found to neutralize MERS-CoV infection efficiently. We also evaluated antibody affinity based on enzyme-linked immunosorbent assay and surface plasmon resonance using S1 antigen. Immunocytochemistry assays showed that mAbs have the specificity to MERS-CoV, not bind to other human coronaviruses. Furthermore, the most potent mAb will be analyzed in MERS-CoV neutralization in vivo human DPPIV knock-in mice model therapuetically or prophylactically. Therefore, our results will be utilized in the preclinical data for the development of MERS-CoV therapeutic or prophylactic antibodies.
This study was supported by grants from the intramural research fund of the Korea national institute of health (2016-NG47001-00).