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

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

Research output: Working paper


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 serological response to SARS-CoV-2 RBD, the SARS-CoV-2 NTD response is less cross-reactive with SARS-CoV. 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 an alternative strategy for serology testing, it may not be suitable as an immunogen for vaccine development.Competing Interest StatementThe authors have declared no competing interest.
Original languageEnglish (US)
PublisherCold Spring Harbor Laboratory Press
Number of pages25
StateIn preparation - Feb 18 2021

Publication series

PublisherCold Spring Harbor Laboratory Press


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


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