The mean OD 450 values calculated after testing each plasma sample in triplicate are shown. (B) Binding of plasma from healthy donors and SARS-CoV-2 infected patients to SARS-CoV-2 spike protein, SARS-CoV-2 RBD protein, SARS-CoV-2 S2 subunit, SARS-CoV spike protein and SARS-CoV RBD protein were measured by ELISA. Regions corresponding to the S1, S2, S2’ subunits, and ectodomain are also indicated. Locations of secretion signal peptide (SP), N-terminal domain (NTD), receptor-binding domain (RBD), S1/S2 cleavage site, fusion peptide (FP), S2’ cleavage site, internal fusion peptide (IFP), heptad repeat 1 (HR1), heptad repeat 1 (HR2), transmembrane domain (TM), and cytoplasmic domain (CP) are indicated. (A) Schematic diagram of the SARS-CoV-2 spike protein. Human serological responses to SARS-CoV-2. Mice infected or immunized with SARS-CoV-2 or SARS-CoV were also used to investigate cross-reactivity of antibody responses between SARS CoV-2 and SARS-CoV. In this study, we examined the antibody responses in 15 patients from Hong Kong who were infected by SARS-CoV-2, and seven by SARS-CoV. So far, data have not yet been reported from polyclonal human sera from patients to evaluate the antibody response elicited by SARS-CoV-2 infection and to determine whether cross-reactive antibody responses between SARS-CoV-2 and SARS-CoV can be generated. However, most monoclonal antibodies tested to date that target the RBD of SARS-CoV have failed to bind to the RBD of SARS-CoV-2 ( Tian et al., 2020 Wrapp et al., 2020), suggesting that the antigenicity of these two viruses to the RBD is quite distinct. ![]() The prefusion structure of the S protein of SARS-CoV-2 has been recently determined by cryo-EM ( Wrapp et al., 2020), and revealed overall structural similarity to that of SARS-CoV. The RBD is also a primary target of the antibody response in humoral immunity and is believed to be the major protective antigen ( Chen et al., 2005). Binding between the receptor-binding domain (RBD) in the S1 subunit and the ACE2 receptor triggers a conformational change in the S protein that subsequently initiates membrane fusion events with the host cell. The S protein forms a homotrimer in which each protomer is composed of two subunits, S1 and S2 ( Figure 1A). The spike glycoprotein (S) on the surface of coronaviruses is essential for virus entry through binding to the ACE2 receptor and viral fusion with the host cell. Moreover, it has been shown that both viruses use the angiotensin-converting enzyme 2 (ACE2) as the receptor for cell entry and infection ( Letko et al., 2020 Li et al., 2003). Phylogenetic analysis has demonstrated that SARS-CoV-2 and SARS CoV, a coronavirus that also caused a global outbreak in 2003, are closely related phylogenetically, with genomic nucleotide sequence identity of around 80% ( Wu et al., 2020 Zhou et al., 2020). ![]() As of 2020 March 15, over 150,000 confirmed cases of SARS-CoV-2 have been reported with close to 6,000 deaths. The emergence of spread of a novel coronavirus SARS-CoV-2 causing severe respiratory disease (COVID-19) has now led to a pandemic with major impact on global health, economy and societal behavior ( Coronaviridae Study Group of the International Committee on Taxonomy of, 2020 Poon and Peiris, 2020 Zhu et al., 2020). ![]() Overall, this study not only addresses a fundamental question regarding the antigenicity differences between SARS-CoV-2 and SARS-CoV, but also has important implications in vaccine Whether these non-neutralizing antibody responses will lead to antibody-dependent disease enhancement needs to be addressed in the future. Our results show that while cross-reactivity in antibody binding to the spike protein is common, cross-neutralization of the live viruses is rare, indicating the presence of non-neutralizing antibody response to conserved epitopes in the spike. We address this question by using plasma from patients infected by SARS-CoV-2 or SARS-CoV, and plasma obtained from infected or immunized mice. One major immunological question is concerning the antigenic differences between SARS-CoV-2 and SARS-CoV. There is currently a lack of knowledge in the antibody response elicited from SARS-CoV-2 infection. The World Health Organization has recently declared the ongoing outbreak of COVID-19, which is caused by a novel coronavirus SARS-CoV-2, as pandemic.
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