26The World Health Organization has recently declared the ongoing outbreak of COVID-27 19, which is caused by a novel coronavirus SARS-CoV-2, as pandemic. There is 28 currently a lack of knowledge in the antibody response elicited from SARS-CoV-2 29 infection. One major immunological question is concerning the antigenic differences 30 between SARS-CoV-2 and SARS-CoV. We address this question by using plasma from 31 patients infected by SARS-CoV-2 or SARS-CoV, and plasma obtained from infected or 32 immunized mice. Our results show that while cross-reactivity in antibody binding to the 33 spike protein is common, cross-neutralization of the live viruses is rare, indicating the 34 presence of non-neutralizing antibody response to conserved epitopes in the spike.
35Whether these non-neutralizing antibody responses will lead to antibody-dependent 36 disease enhancement needs to be addressed in the future. Overall, this study not only 37 addresses a fundamental question regarding the antigenicity differences between 38 SARS-CoV-2 and SARS-CoV, but also has important implications in vaccine 39 development. : bioRxiv preprint 4 polyclonal human sera from patients to evaluate the antibody response elicited by 67 SARS-CoV-2 infection and to determine whether cross-reactive antibody responses 68 between SARS-CoV-2 and SARS-CoV can be generated. In this study, we examined the 69 antibody responses in 15 patients from Hong Kong who were infected by SARS-CoV-2, 70 and seven by SARS-CoV. Mice infected or immunized with SARS-CoV-2 or SARS-CoV 71 were also used to investigate cross-reactivity of antibody responses between SARS-72 CoV-2 and SARS-CoV. 73 74 Results 75 Patient samples show cross-reactivity in binding 76 Fifteen heparin anticoagulated plasma samples (from day 2 to 22 post-symptom onset) 77 from SARS-CoV-2 infected patients were analyzed (Table S1). Binding of plasma to the 78 S ectodomain and RBD of both SARS-CoV-2 and SARS-CoV (see Methods) was 79 measured by ELISA ( Figure 1B, Figure S1). Plasma samples from healthy donors 80 collected from the Hong Kong Red Cross served as controls. As compared to the 81 plasma from healthy donors, plasma from patients from day 10 post-symptom onward 82 reacted strongly in ELISA binding assays to the S ectodomain (p-value < 2e-16, two-83 tailed t-test) and RBD (p-value = 2e-13, two-tailed t-test) of SARS-CoV-2. Interestingly, 84 the plasma from SARS-CoV-2-infected patients could also cross-react, although less 85 strongly, with the SARS-CoV S ectodomain (p-value = 8e-06, two-tailed t-test) and the 86 SARS-CoV RBD (p-value = 0.048, two-tailed t-test) ( Figure 1B). Nevertheless, only five 87 of the samples from the SARS-CoV-2-infected patients had convincing antibody binding 88 responses to the SARS-CoV RBD. The other plasma reacted more weakly or not at all 89 with the SARS-CoV RBD ( Figure 1B). This result indicates that the cross-reactive 90 antibody response to the S protein after SARS-CoV-2 infection mostly targets non-RBD 91 regions. Consistent with that observation, reactivi...