SARS-CoV-2 variant with higher affinity to ACE2 shows reduced sera neutralization susceptibility

Vogel, Monique; Chang, Xinyue; Augusto, Gilles; Mo, Mohsen; Speiser, Daniel E.; Mf, Bachmann

doi:10.1101/2021.03.04.433887

Cited by 3 publications

(2 citation statements)

References 23 publications

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“…There is some evidence that protection from reinfection can be very short-lived, as demonstrated by some patients who experienced COVID-19 twice, despite a proven virus-free interval in between [36][37][38]. In addition, some of the recently emerging mutated viruses of concern seem to escape antibody-mediated recognition of the RBD almost completely [39][40][41]. Thus, on average, SARS-CoV-2 triggers a curiously weak and short-lived response, while most other acute disease-causing viruses induce long-lived neutralizing antibody responses [42].…”

Section: Discussionmentioning

confidence: 99%

Development of a Vaccine against SARS-CoV-2 Based on the Receptor-Binding Domain Displayed on Virus-Like Particles

et al. 2021

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The ongoing coronavirus disease (COVID-19) pandemic is caused by a new coronavirus (severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)) first reported in Wuhan City, China. From there, it has been rapidly spreading to many cities inside and outside China. Nowadays, more than 110 million cases with deaths surpassing 2 million have been recorded worldwide, thus representing a major health and economic issues. Rapid development of a protective vaccine against COVID-19 is therefore of paramount importance. Here, we demonstrated that the recombinantly expressed receptor-binding domain (RBD) of the spike protein can be coupled to immunologically optimized virus-like particles derived from cucumber mosaic virus (CuMVTT). The RBD displayed CuMVTT bound to ACE2, the viral receptor, demonstrating proper folding of RBD. Furthermore, a highly repetitive display of the RBD on CuMVTT resulted in a vaccine candidate that induced high levels of specific antibodies in mice, which were able to block binding of the spike protein to ACE2 and potently neutralize SARS-CoV-2 virus in vitro.

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Section: Discussionmentioning

confidence: 99%

Development of a Vaccine against SARS-CoV-2 Based on the Receptor-Binding Domain Displayed on Virus-Like Particles

et al. 2021

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“…All three VOC harbor an N501Y mutation within S-RBD, while the 501Y.V2 and P.1 variants contain two additional RBD changes, K417N/T and E484K. These mutations, located at the interfaces of the RBD-ACE2/antibody complexes, have been shown to increase Spike binding to ACE2 and decrease its recognition by neutralizing antibodies (Nab) (28,(43)(44)(45), leading to the enhanced infection efficacy and transmissibility for the variants. Intriguingly, the same amino acid changes have been shown to alter the corresponding epitopes targeted by neutralizing antibodies (28), thereby providing a potential mechanism of immune escape by reducing or disabling antibody-mediated neutralization (43,(46)(47)(48).…”

Section: Discussionmentioning

confidence: 99%

Epitope-specific antibody responses differentiate COVID-19 outcomes and variants of concern

Voss¹,

Esmail²,

Liu³

et al. 2021

JCI Insight

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BACKGROUND. The role of humoral immunity in the coronavirus disease 2019 (COVID-19) is not fully understood owing, in large part, to the complexity of antibodies produced in response to the SARS-CoV-2 infection. There is a pressing need for serology tests to assess patient-specific antibody response and predict clinical outcome. METHODS. Using SARS-CoV-2 proteome and peptide microarrays, we screened 146 COVID-19 patients plasma samples to identify antigens and epitopes. This enabled us to develop a master epitope array and an epitope-specific agglutination assay to gauge antibody responses systematically and with high resolution. RESULTS. We identified linear epitopes from the Spike (S) and Nucleocapsid (N) protein and showed that the epitopes enabled higher resolution antibody profiling than the S or N protein antigen. Specifically, we found that antibody responses to the S(811-825), S(881-895) and N(156-170) epitopes negatively or positively correlated with clinical severity or patient survival. Moreover, we found that the P681H and S235F mutations associated with the coronavirus variant of concern B.1.1.7 altered the specificity of the corresponding epitopes. CONCLUSIONS. Epitope-resolved antibody testing not only affords a high-resolution alternativeto conventional immunoassays to delineate the complex humoral immunity to SARS-CoV-2 and differentiate between neutralizing and non-neutralizing antibodies, it may potentially be used to predict clinical outcome. The epitope peptides can be readily modified to detect antibodies against variants of concern (VOC) in both the peptide array and latex agglutination formats.

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AP205 VLPs Based on Dimerized Capsid Proteins Accommodate RBM Domain of SARS-CoV-2 and Serve as an Attractive Vaccine Candidate

et al. 2021

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COVID-19 is a novel disease caused by SARS-CoV-2 which has conquered the world rapidly resulting in a pandemic that massively impacts our health, social activities, and economy. It is likely that vaccination is the only way to form “herd immunity” and restore the world to normal. Here we developed a vaccine candidate for COVID-19 based on the virus-like particle AP205 displaying the spike receptor binding motif (RBM), which is the major target of neutralizing antibodies in convalescent patients. To this end, we genetically fused the RBM domain of SARS-CoV-2 to the C terminus of AP205 of dimerized capsid proteins. The fused VLPs were expressed in E. coli, which resulted in insoluble aggregates. These aggregates were denatured in 8 M urea followed by refolding, which reconstituted VLP formation as confirmed by electron microscopy analysis. Importantly, immunized mice were able to generate high levels of IgG antibodies recognizing eukaryotically expressed receptor binding domain (RBD) as well as spike protein of SARS-CoV-2. Furthermore, induced antibodies were able to neutralize SARS-CoV-2/ABS/NL20. Additionally, this vaccine candidate has the potential to be produced at large scale for immunization programs.

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SARS-CoV-2 variant with higher affinity to ACE2 shows reduced sera neutralization susceptibility

Cited by 3 publications

References 23 publications

Development of a Vaccine against SARS-CoV-2 Based on the Receptor-Binding Domain Displayed on Virus-Like Particles

Development of a Vaccine against SARS-CoV-2 Based on the Receptor-Binding Domain Displayed on Virus-Like Particles

Epitope-specific antibody responses differentiate COVID-19 outcomes and variants of concern

AP205 VLPs Based on Dimerized Capsid Proteins Accommodate RBM Domain of SARS-CoV-2 and Serve as an Attractive Vaccine Candidate

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