Homologous and heterologous serological response to the N-terminal domain of SARS-CoV-2 in humans and mice

Huibin Lv, Owen Tak-Yin Tsang, Ray T Y So, Yiquan Wang, Meng Yuan, Hejun Liu, Garrick K Yip, Qi Wen Teo, Yihan Lin, Weiwen Liang, Jinlin Wang, Wilson W Ng, Ian A Wilson, J S Malik Peiris, Nicholas C Wu, Chris K P Mok

Research output: Contribution to journalArticlepeer-review


The increasing numbers of infected cases of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses serious threats to public health and the global economy. Most SARS-CoV-2 neutralizing antibodies target the receptor binding domain (RBD) and some the N-terminal domain (NTD) of the spike protein, which is the major antigen of SARS-CoV-2. While the antibody response to RBD has been extensively characterized, the antigenicity and immunogenicity of the NTD protein are less well studied. Using 227 plasma samples from COVID-19 patients, we showed that SARS-CoV-2 NTD-specific antibodies could be induced during infection. As compared to the results of SARS-CoV-2 RBD, the serological response of SARS-CoV-2 NTD is less cross-reactive with SARS-CoV, a pandemic strain that was identified in 2003. Furthermore, neutralizing antibodies are rarely elicited in a mice model when NTD is used as an immunogen. We subsequently demonstrate that NTD has an altered antigenicity when expressed alone. Overall, our results suggest that while NTD offers a supplementary strategy for serology testing, it may not be suitable as an immunogen for vaccine development.

Original languageEnglish (US)
Pages (from-to)2296-2305
Number of pages10
JournalEuropean Journal of Immunology
Issue number9
Early online dateJun 5 2021
StatePublished - Sep 2021


  • COVID-19
  • serology
  • immunogen
  • SARS-CoV-2
  • NTD
  • N-terminal domain

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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