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- Title
Breadth and function of antibody response to acute SARS-CoV-2 infection in humans.
- Authors
Huang, Kuan-Ying A.; Tan, Tiong Kit; Chen, Ting-Hua; Huang, Chung-Guei; Harvey, Ruth; Hussain, Saira; Chen, Cheng-Pin; Harding, Adam; Gilbert-Jaramillo, Javier; Liu, Xu; Knight, Michael; Schimanski, Lisa; Shih, Shin-Ru; Lin, Yi-Chun; Cheng, Chien-Yu; Cheng, Shu-Hsing; Huang, Yhu-Chering; Lin, Tzou-Yien; Jan, Jia-Tsrong; Ma, Che
- Abstract
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 13.0% of plasmablast-derived MAbs were reactive with virus spike glycoprotein or nucleocapsid, respectively. A subset of anti-spike (10 of 32) and over half of anti-nucleocapsid (19 of 35) 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. At last, 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. Author summary: The global COVID-19 outbreak poses a serious threat to human health and antibody-mediated immunity plays a key role in controlling acute viral infection in humans. We report the complete mapping of antibody responses, from serology through to single plasmablast-derived antibody clone, in three COVID-19 patients with different severities. The data show that a subset of anti-spike antibodies and more than half of anti-nucleocapsid plasmablast-derived antibodies cross-react with other betacoronaviruses including human coronavirus OC43, which suggests an expansion of memory B cells upon SARS-CoV-2 infection. Anti-SARS-CoV-2 spike antibody clones target a diverse spectrum of epitopes on the receptor-binding domain (RBD), non-RBD S1 and S2 regions of the spike glycoprotein, 40% of them neutralise wild-type SARS-CoV-2. Anti-RBD antibodies constitute one major part of neutralising antibodies, potent antibodies target three non-overlapping epitopes on the RBD, and the neutralising activity is linked to ACE2-binding blockade. Combination of multiple antibody clones targeting non-overlapping epitopes offer a potential avenue to combat the global outbreak.
- Subjects
ANTIBODY formation; SARS-CoV-2; COVID-19 pandemic; MONOCLONAL antibodies; COVID-19
- Publication
PLoS Pathogens, 2021, Vol 17, Issue 2, p1
- ISSN
1553-7366
- Publication type
Article
- DOI
10.1371/journal.ppat.1009352