Antibodies in serum samples collected from patients infected with SARS-CoV during the 2003 outbreak effectively neutralized SARS-CoV-2 infection in cultured cells, according to a new study. The authors also report that, surprisingly, mice and rabbits immunized with a receptor binding domain (RBD) from a strain of SARS-CoV that infects the Himalayan palm civet elicited stronger antibody responses against SARS-CoV-2 than animals immunized with an RBD from a human SARS-CoV strain.
The authors suggest that their findings may inform strategies to develop universal vaccines against emerging and future coronaviruses. Yuanmei Zhu and colleagues analyzed 20 convalescent serum samples from patients infected with SARS-CoV, determining cross-reactivity for protein antigens derived from four regions of the SARS-CoV-2 spike protein, including the S ectodomain (S), S1 subunit, RBD, and S2 subunit.
While all serum samples reacted strongly with the S and S2 proteins, they reacted more weakly with the S1 and RBD proteins. A separate test using a single-cycle infection assay determined that the convalescent SARS-CoV sera efficiently prevented both SARS-CoV and SARS-CoV-2 pseudoviruses (which cannot produce viral surface proteins on their own) from infecting cells, although they inhibited SARS-CoV-2 activity less efficiently.
The researchers verified their findings in animals and specifically characterized the RBD's ability to mediate cross-reactivity in mice, since the RBD is the least conserved of the spike protein sites between the two viruses. They found that anti-RBD serum from SARS-CoV cross-reacted well with SARS-CoV-2, suggesting a key antigen component is genetically conserved in the RBD sites of the two viruses. Zhu et al. note that although antibody-dependent enhancement (when binding a virus to certain antibodies actually eases its entry into host cells) was not observed in this study, the effect should be addressed during vaccine development.
Zhu, Y., et al. (2020) Cross-reactive neutralization of SARS-CoV-2 by serum antibodies from recovered SARS patients and immunized animals. Science Advances. doi.org/10.1126/sciadv.abc9999.