Journal Article

Breadth and function of antibody response to acute SARS-CoV-2 infection in humans

Liu, Xu, Huang, Chung-Guei, Lin, Yi-Chun, Chen, Cheng-Pin, Harding, Adam, Daniels, Rodney S., Jan, Jia-Tsrong, Harvey, Ruth, Ma, Che, Rijal, Pramila, Schimanski, Lisa, James, William, Chen, Ting-Hua, Hussain, Saira, Tan, Tiong Kit, Shih, Shin-Ru, Cheng, Chien-Yu, Huang, Kuan-Ying A., Cheng, Shu-Hsing, Knight, Michael, Huang, Yhu-Chering, Gilbert-Jaramillo, Javier, Townsend, Alain R., McCauley, John W., Lin, Tzou-Yien

2021

Overview

Serological and plasmablast responses and plasmablast-derived IgG monoclonal antibodies (MAbs) have been analysed in three COVID-19 patients with different clinical severities. Potent humoral responses were detected within 3 weeks of onset of illness in all patients and the serological titre was elicited soon after or concomitantly with peripheral plasmablast response. An average of 13.7% and 3.5% of plasmablast-derived MAbs were reactive with virus spike glycoprotein or nucleocapsid, respectively. A subset of anti-spike (10 of 32) antibodies cross-reacted with other betacoronaviruses tested and harboured extensive somatic mutations, indicative of an expansion of memory B cells upon SARS-CoV-2 infection. Fourteen of 32 anti-spike MAbs, including five anti-receptor-binding domain (RBD), three anti-non-RBD S1 and six anti-S2, neutralised wild-type SARS-CoV-2 in independent assays. Anti-RBD MAbs were further grouped into four cross-inhibiting clusters, of which six antibodies from three separate clusters blocked the binding of RBD to ACE2 and five were neutralising. All ACE2-blocking anti-RBD antibodies were isolated from two recovered patients with prolonged fever, which is compatible with substantial ACE2-blocking response in their sera. Finally, the identification of non-competing pairs of neutralising antibodies would offer potential templates for the development of prophylactic and therapeutic agents against SARS-CoV-2.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: ACE2 / Adult / Angiotensin-converting enzyme 2 / Angiotensin-Converting Enzyme 2 - antagonists & inhibitors / Angiotensin-Converting Enzyme 2 - immunology / Antibodies / Antibodies, Monoclonal - immunology / Antibodies, Neutralizing - immunology / Antibodies, Viral - blood / Antibodies, Viral - genetics / Antibodies, Viral - immunology / Antibody response / Antibody-Producing Cells - immunology / Antigens / Binding / Binding Sites / Biology and life sciences / Cell membranes / Coronaviruses / COVID-19 / COVID-19 - immunology / Domains / Epitopes / Flow cytometry / Glycoproteins / Humans / Illnesses / Immunoglobulin G / Immunoglobulin G - immunology / Infections / Influenza / Laboratories / Medicine and health sciences / Membrane fusion / Middle East respiratory syndrome / Monoclonal antibodies / Mutation / Nucleocapsid - immunology / Nucleocapsids / Pandemics / Patients / Polypeptides / Receptors / Research and Analysis Methods / Respiratory diseases / SARS-CoV-2 - immunology / Serology / Severe acute respiratory syndrome / Severe acute respiratory syndrome coronavirus 2 / Spike glycoprotein / Spike Glycoprotein, Coronavirus - immunology / Vaccines / Viral diseases / Viruses