Breadth and function of antibody response to acute SARS-CoV-2 infection in humans.
journal contributionposted on 26.05.2021, 09:36 by Kuan-Ying A Huang, Tiong Kit Tan, Ting-Hua Chen, Chung-Guei Huang, Ruth Harvey, Saira Hussain, Cheng-Pin Chen, Adam Harding, Javier Gilbert-Jaramillo, Xu Liu, Michael Knight, Lisa Schimanski, Shin-Ru Shih, Yi-Chun Lin, Chien-Yu Cheng, Shu-Hsing Cheng, Yhu-Chering Huang, Tzou-Yien Lin, Jia-Tsrong Jan, Che Ma, William James, Rodney S Daniels, John W McCauley, Pramila Rijal, Alain R Townsend
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.