Lack of antibody-mediated cross-protection between SARS-CoV-2 and SARS-CoV infections

Abstract

Background The novel coronavirus (SARS-CoV-2) shares approximately 80% whole genome sequence identity and 66% spike (S) protein identity with that of SARS-CoV. The cross-neutralization between these viruses is currently not well-defined. Methods Here, by using the live SARS-CoV-2 virus infection assay as well as HIV-1 based pseudotyped-virus carrying the spike (S) gene of the SARS-CoV-2 (ppSARS-2) and SARS-CoV (ppSARS), we examined whether infections with SARS-CoV and SARS-CoV-2 can induce cross-neutralizing antibodies. Findings We confirmed that SARS-CoV-2 infects cells via angiotensin converting enzyme 2 (ACE2), the functional receptor for SARS-CoV, and we also found that the recombinant receptor binding domain (RBD) of the S protein of SARS-CoV effectively inhibits ppSARS-2 entry in Huh7.5 cells. However, convalescent sera from SARS-CoV and SARS-CoV-2 patients showed high neutralizing activity only against the homologous virus, with no or limited cross-neutralization activity against the other pseudotyped virus. Similar results were also observed in vaccination studies in mice. Interpretation Our study demonstrates that although both SARS-CoV and SARS-CoV-2 use ACE2 as a cellular receptor, the neutralization epitopes are not shared by these two closely-related viruses, highlighting challenges towards developing a universal vaccine against SARS-CoV related viruses. Funding This work was supported by the National Key Research and Development Program of China, the National Major Project for Control and Prevention of Infectious Disease in China, and the One Belt and One Road Major Project for infectious diseases.

A longitudinal study of SARS-CoV-2-infected patients reveals a high correlation between neutralizing antibodies and COVID-19 severity

“…Furthermore, cross-neutralization of SARS-CoV-2 can be induced by sera from convalescent SARS-CoV patients, which is likely due to high homology between these two viruses, though it seems to be serum dependent. 56 , 57 Thus, our results indicate an absence of cross-neutralization between SARS-CoV-2 and other endemic human coronaviruses, suggesting that nAbs or other non-nAbs 6 generated by previous infections with other coronaviruses do not protect against SARS-CoV-2 infection.…”

The SARS-CoV-2 Spike Glycoprotein Biosynthesis, Structure, Function, and Antigenicity: Implications for the Design of Spike-Based Vaccine Immunogens

“…Theoretically, the native HIV-1 Env trimer present on the surface of intact virions is thought to be a most ideal immunogen (60), as most of the neutralizing antibodies thus far described could recognize and bind to the prefusion form of trimeric HIV-1 Env, although it is with great difficulty that such neutralizing antibodies against this glycan-covered, sequence-variable native form are induced (36). For SARS-CoV-2, different lines of research have shown that convalescent sera from SARS-CoV and SARS-CoV-2 patients showed no or limited crossneutralization activity against these two viruses by pseudotyped and authentic viral infection assays, despite significant crossreactivity in binding to the S glycoproteins of both viruses (9,(79)(80)(81). Similar results were also observed in infected or immunized animals (48,79,81).…”

“…For SARS-CoV-2, different lines of research have shown that convalescent sera from SARS-CoV and SARS-CoV-2 patients showed no or limited crossneutralization activity against these two viruses by pseudotyped and authentic viral infection assays, despite significant crossreactivity in binding to the S glycoproteins of both viruses (9,(79)(80)(81). Similar results were also observed in infected or immunized animals (48,79,81). Together with the finding that although the SARS-CoV-2 S protein shares a high degree of amino acid sequence identity with that of SARS-CoV (~76% overall), the RBM is less conserved (~47% identity) than any other functional region or domain (82), it can thus been surmised that the RBM has the most immunodominant neutralizing epitope(s) of the whole S protein, capable of readily eliciting strong neutralizing antibody responses.…”

Ferritin nanoparticle based SARS-CoV-2 RBD vaccine induces persistent antibody response and long-term memory in mice

“…The experiment was conducted in a BSL-3 laboratory, as previously reported 25–28 . Briefly, the sera were 2-fold serially diluted using 2% FBS-DMEM and mixed with the same volume of live SARS-CoV-2 (C-Tan-nCoV strain 04, 100TCID50), the mixtures were incubated at 37 °C for 1 h, following which they were added to the seeded Vero cells.…”