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

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 MaWilliam James, Rodney S. Daniels, John W. McCauley, Pramila Rijal, Alain R. Townsend

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

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.

Original languageEnglish
Article numbere1009352
JournalPLoS Pathogens
Volume17
Issue number2
DOIs
Publication statusPublished - Feb 26 2021

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

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