tetano
Editor, Senior Moderator
PLoS One. 2020 May 8;15(5):e0232757. doi: 10.1371/journal.pone.0232757. eCollection 2020.
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 JH[SUP]1[/SUP], Woo HM[SUP]2[/SUP], Lee TY[SUP]2[/SUP], Lee SY[SUP]2[/SUP], Shim SM[SUP]2[/SUP], Park WJ[SUP]2[/SUP], Yang JS[SUP]2[/SUP], Kim JA[SUP]3[/SUP], Yun MR[SUP]3[/SUP], Kim DW[SUP]3[/SUP], Kim SS[SUP]4[/SUP], Zhang Y[SUP]5[/SUP], Shi W[SUP]5[/SUP], Wang L[SUP]5[/SUP], Graham BS[SUP]5[/SUP], Mascola JR[SUP]5[/SUP], Wang N[SUP]6[/SUP], McLellan JS[SUP]6[/SUP], Lee JY[SUP]2[/SUP], Lee H[SUP]2[/SUP].
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Abstract
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.
PMID:32384116DOI:10.1371/journal.pone.0232757
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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 JH[SUP]1[/SUP], Woo HM[SUP]2[/SUP], Lee TY[SUP]2[/SUP], Lee SY[SUP]2[/SUP], Shim SM[SUP]2[/SUP], Park WJ[SUP]2[/SUP], Yang JS[SUP]2[/SUP], Kim JA[SUP]3[/SUP], Yun MR[SUP]3[/SUP], Kim DW[SUP]3[/SUP], Kim SS[SUP]4[/SUP], Zhang Y[SUP]5[/SUP], Shi W[SUP]5[/SUP], Wang L[SUP]5[/SUP], Graham BS[SUP]5[/SUP], Mascola JR[SUP]5[/SUP], Wang N[SUP]6[/SUP], McLellan JS[SUP]6[/SUP], Lee JY[SUP]2[/SUP], Lee H[SUP]2[/SUP].
Author information
Abstract
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.
PMID:32384116DOI:10.1371/journal.pone.0232757
Free full text