Cross-reactive Antibody Response between SARS-CoV-2 and SARS-CoV Infections

Lv, Huibin; Wu, Nicholas C.; Tsang, Owen Tak Yin; Yuan, Meng; Perera, Ranawaka A.P.M.; Leung, Wai Shing; So, Ray T.Y.; Chan, Jacky Man Chun; Yip, Garrick K.; Chik, Thomas Shiu Hong; Wang, Yiquan; Choi, Chris Yau Chung; Lin, Yihan; Ng, Wilfred; Zhao, Jincun; Poon, Leo L M; Peiris, J. S. Malik; Wilson, Ian A.; Mok, Chris Ka Pun

doi:10.1016/j.celrep.2020.107725

Cited by 387 publications

(414 citation statements)

References 49 publications

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“…We tested samples #1, 2 and 3, which had the highest NT50 and NT80. None of these sera had detectable neutralizing activity (NT50 <25) against the SARS-CoV-1 pseudotype, which is consistent with previous reports [10][11][12] . As a positive control and also as a standard to monitor variability between neutralization experiments, we used recombinant soluble receptor binding domain from SARS-CoV-2 spike protein.…”

supporting

confidence: 91%

Neutralization Assay with SARS-CoV-1 and SARS-CoV-2 Spike Pseudotyped Murine Leukemia Virions

Zheng

Larragoite

Lama³

et al. 2020

Preprint

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Antibody neutralization is an important prognostic factor in many viral diseases. To easily and rapidly measure titers of neutralizing antibodies in serum or plasma, we developed pseudovirion particles composed of the spike glycoprotein of SARS-CoV-2 incorporated onto murine leukemia virus capsids and a modified minimal MLV genome encoding firefly luciferase. These pseudovirions provide a practical means of assessing immune responses under laboratory conditions consistent with biocontainment level 2.

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supporting

confidence: 91%

Neutralization Assay with SARS-CoV-1 and SARS-CoV-2 Spike Pseudotyped Murine Leukemia Virions

Zheng

Larragoite

Lama³

et al. 2020

Preprint

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“…First, the mice were transfected with 10 μg of mRNA encoding either hACE2 or GFP as a control. Twentyfour hours after mRNA in vivo delivery, we infected the hACE2 or GFP transfected Ifnar1 -/mice with 5x10 4 focus forming units (FFU) per mouse of SARS-CoV-2 administered both intravenously (IV) and intranasally (IN). Blood was collected eight days post infection for acute phase T cell analysis.…”

Section: Adaptive Immune Response To Sars-cov-2mentioning

confidence: 99%

“…Interestingly, comparison at the amino acid level shows an approximate 77% identity, with the divergence of amino acids not localized to particular proteins shared between the two viruses. The similarities between SARS CoV and SARS CoV-2 have led to evidence of considerable serological cross-reactivity [4].…”

Section: Introductionmentioning

confidence: 99%

mRNA induced expression of human angiotensin-converting enzyme 2 in mice for the study of the adaptive immune response to severe acute respiratory syndrome coronavirus 2

Hassert

Geerling

Stone

et al. 2020

Preprint

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The novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic resulting in nearly 20 million infections across the globe, as of August 2020. Critical to the rapid evaluation of vaccines and antivirals is the development of tractable animal models of infection. The use of common laboratory strains of mice to this end is hindered by significant divergence of the angiotensin-converting enzyme 2 (ACE2), which is the receptor required for entry of SARS-CoV-2. In the current study, we designed and utilized an mRNA-based transfection system to induce expression of the hACE2 receptor in order to confer entry of SARS-CoV-2 in otherwise non-permissive cells. By employing this expression system in an in vivo setting, we were able to interrogate the adaptive immune response to SARS-CoV-2 in type 1 interferon receptor deficient mice. In doing so, we showed that the T cell response to SARS-CoV-2 is enhanced when hACE2 is expressed during infection. Moreover, we demonstrated that these responses are preserved in memory and are boosted upon secondary infection. Interestingly, we did not observe an enhancement of SARS-CoV-2 specific antibody responses with hACE2 induction. Importantly, using this system, we functionally identified the CD4+ and CD8+ peptide epitopes targeted during SARS-CoV-2 infection in H2b restricted mice. Antigen-specific CD8+ T cells in mice of this MHC haplotype primarily target peptides of the spike and membrane proteins, while the antigen-specific CD4+ T cells target peptides of the nucleocapsid, membrane, and spike proteins. The functional identification of these T cell epitopes will be critical for evaluation of vaccine efficacy in murine models of SARS-CoV-2. The use of this tractable expression system has the potential to be used in other instances of emerging infections in which the rapid development of an animal model is hindered by a lack of host susceptibility factors.

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“…Since the S protein is essential for virus entry through engaging the host receptor and mediating virus-host membrane fusion, many antibodies to the S protein are neutralizing [1][2][3][4][5][6][7][8][9][10][11][12]. The S proteins of SARS-CoV-2 and SARS-CoV, which caused a global outbreak in 2003, have an amino-acid sequence identity of around 77% [13] that leads to differences in antigenicity in serology studies [14,15]. Although a few monoclonal antibodies have been discovered that can cross-neutralize SARS-CoV and SARS-CoV-2 [6,7,16,17], they seem to be relatively rare in COVID-19 patients [1,3,4,14].…”

Section: Introductionmentioning

confidence: 99%

A natural mutation between SARS-CoV-2 and SARS-CoV determines neutralization by a cross-reactive antibody

Yuan

Bangaru

et al. 2020

Preprint

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Epitopes that are conserved among SARS-like coronaviruses are attractive targets for design of cross-reactive vaccines and therapeutics. CR3022 is a SARS-CoV neutralizing antibody to a highly conserved epitope on the receptor binding domain (RBD) on the spike protein that can cross-react with SARS-CoV-2, but with lower affinity. Using x-ray crystallography, mutagenesis, and binding experiments, we illustrate that of four amino acid differences in the CR3022 epitope between SARS-CoV-2 and SARS-CoV, a single mutation P384A fully determines the affinity difference. CR3022 does not neutralize SARS-CoV-2, but the increased affinity to SARS-CoV-2 P384A mutant now enables neutralization with a similar potency to SARS-CoV. We further investigated CR3022 interaction with the SARS-CoV spike protein by negative-stain EM and cryo-EM. Three CR3022 Fabs bind per trimer with the RBD observed in different up-conformations due to considerable flexibility of the RBD. In one of these conformations, quaternary interactions are made by CR3022 to the N-terminal domain (NTD) of an adjacent subunit. Overall, this study provides insights into antigenic variation and potential for cross-neutralizing epitopes on SARS-like viruses.

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Cross-reactive Antibody Response between SARS-CoV-2 and SARS-CoV Infections

Abstract: Highlights d Cross-reactive antigen binding is common between SARS-CoV and SARS-CoV-2 d Cross-reactive antibody responses target both RBD and non-RBD regions d Cross-neutralization of live viruses may be rare between SARS-CoV and SARS-CoV-2

Cited by 387 publications

References 49 publications

Neutralization Assay with SARS-CoV-1 and SARS-CoV-2 Spike Pseudotyped Murine Leukemia Virions

Neutralization Assay with SARS-CoV-1 and SARS-CoV-2 Spike Pseudotyped Murine Leukemia Virions

mRNA induced expression of human angiotensin-converting enzyme 2 in mice for the study of the adaptive immune response to severe acute respiratory syndrome coronavirus 2

A natural mutation between SARS-CoV-2 and SARS-CoV determines neutralization by a cross-reactive antibody

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