Featured COVID-19 Publications
Mor, M. et al. Multi-clonal SARS-CoV-2 neutralization by antibodies isolated from severe COVID-19 convalescent donors. PLoS Pathog 17(2): e1009165. 2021.
The relationship between antibodies, immune cells and disease severity in SARS-CoV-2 cases is not fully known. This study analyzes the cellular, molecular, and functional features of the antibody response in convalescent blood from severe versus mild SARS-CoV-2 donors. The authors used the Incucyte® S3 Live-Cell Analysis System to monitor cell death and cell-to-cell fusion when using isolated anti-SARS-CoV-2 antibodies. The data showed that severe COVID-19 triggers a unique antibody response and can inform treatment strategies with antibody cocktails.
- Donors with severe disease exhibited higher titers of anti-SARS-CoV-2 IgG against spike receptor binding domain (RBD), and higher B-cell expansion.
- Six out of 22 isolated monoclonal antibodies potently neutralized the live virus and prevented syncytia formation in live-cell assays. Peptide libraries, computational methods and mutagenesis analysis revealed the mechanism of antibody binding.
- Cocktails of isolated neutralizing antibodies prevented viral replication in cell culture.
Stukalov, A. et at. Multi-level proteomics reveals host-perturbation strategies of SARS-CoV-2 and SARS-CoV, 2020. doi: https://doi.org/10.1101/2020.06.17.156455
Developing treatments against SARS-CoV2 requires a better understanding of how viral proteins interact with host proteins. This proteomics study characterizes the viral-host protein-protein interactions and signaling processes that are involved in an infection with SARS-CoV-2 and related coronaviruses. The data revealed unique and common pathways that can be manipulated by known drugs to alter the course of infection with coronaviruses.
- Proteomics analysis identified 1,484 interactions between 1,086 cellular proteins and 24 SARS-CoV-2 and 27 SARS-CoV bait proteins, suggesting involvement of a range of biological processes.
- Combined datasets showed that key pathways such as stress and DNA damage response, and regulation of transcription and cell junction organization were involved in the course of infection.
- Selective targeting of these pathways using 48 clinically approved compounds identified kinase and matrix metalloproteinase inhibitors with significant antiviral activity against SARS-CoV2. The authors performed the time-lapse fluorescent viral assays using the Incucyte® S3 Live-Cell Analysis System.
Dogan, M. et al. SARS-CoV-2 specific antibody and neutralization assays reveal the wide range of the humoral immune response to virus. Commun Biol. 4(1):129. 2021.
Understanding the quantity, quality, and duration of antibody response to COVID-19 is critical for the development of vaccines. This study addresses a major gap in these efforts by developing highly sensitive and specific assays for detecting SARS-CoV-2 antibodies and neutralization. Screening for antibody binding to SARS-CoV-2 proteins was performed on an iQue® system for advanced high throughput flow cytometry. The authors used the assays to demonstrate varied humoral immune responses across COVID-19 patients.
- Bead-based fluorescent immunoassay accurately detected SARS-CoV-2 spike protein or nucleocapsid protein specific IgG antibodies at dilutions up to 100,000-fold of plasma samples from SARS-CoV-2 subjects. Other antibody isotypes were also detectable.
- Robust assay using SARS-CoV-2 spike protein pseudovirus detected neutralization in both COVID-19 and convalescent plasma at up to 10,000-fold dilution.
- The assays revealed differences in humoral immune response in COVID-19 patients; namely patients with severe disease had 3,000-fold higher antibody and neutralization titers compared to outpatient or convalescent plasma donors.
Hattori, T. et al. The ACE2-binding Interface of SARS-CoV-2 Spike Inherently Deflects Immune Recognition. J Mol Biol. 433(3):166748. 2021.
A detailed understanding of the immunogenic surfaces on the SARS-CoV-2 spike protein and its receptor binding domain (RBD) is vital for developing potent vaccines and antibody-based treatments. This study utilizes an RBD mutant as tool for characterizing anti-RBD antibodies from convalescent sera of COVID-19 patients. The data showed that the ACE2-interacting surface of the RBD is less immunogenic than other regions. The authors used the iQue® system for advanced high throughput flow cytometry to perform cell- and bead-based binding assays.
- Binding analysis of antibodies in convalescent sera showed that most antibodies did not target the ACE2-interacting surface of RBD.
- An unbiased in vitro antibody selection using a human antibody phage display library showed that 89% of the clones bound the spike protein, but not the RBD or the ACE2-binding surface. The biased screen identified antibodies that targeted the ACE2-binding surface.
- The antibodies that bound RBD in an unbiased selection, preferentially bound the surfaces that are not exposed in the native spike protein trimer.