Coronavirus disease 2019 and the revival of passive immunization: Antibody therapy for inhibiting severe acute respiratory syndrome coronavirus 2 and preventing host cell infection: IUPHAR review 31

Levi‐Schaffer, Francesca; Marco, Ario de

doi:10.1111/bph.15359

Cited by 11 publications

(9 citation statements)

References 125 publications

(165 reference statements)

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“…A crucial unknown at this time is what immune responses are associated with protective immunity. While there is mixed evidence supporting the efficacy of convalescent-phase sera infusion for disease shortening, recent studies suggest that passive infusion of monoclonal antibodies can alter COVID-19 progression ( 8 , 9 ). In order to determine what constitutes protective immunity, well-standardized, reproducible antibody assays are required to establish correlates of risk and protection.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Cell-Based and Surrogate SARS-CoV-2 Neutralization Assays

et al. 2021

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Determinants of protective immunity against SARS-CoV-2 infection require the development of well-standardized, reproducible antibody assays. This need has led to the emergence of a variety of neutralization assays. Head-to-head evaluation of different SARS-CoV-2 neutralization platforms could facilitate comparisons across studies and laboratories. Five neutralization assays were compared using forty plasma samples from convalescent individuals with mild-to-moderate COVID-19: four cell-based systems using either live recombinant SARS-CoV-2 or pseudotyped viral particles created with lentivirus (LV) or vesicular stomatitis virus (VSV) packaging and one surrogate ELISA-based test that measures inhibition of the spike protein receptor binding domain (RBD) binding its receptor, human angiotensin converting enzyme 2 (hACE2). Vero, Vero E6, HEK293T expressing hACE2, and TZM-bl cells expressing hACE2 and transmembrane serine protease 2 were tested. All cell-based assays showed 50% neutralizing dilution (ND50) geometric mean titers (GMTs) that were highly correlated (Pearson r = 0.81–0.89) and ranged within 3.4-fold. The live-virus assay and LV-pseudovirus assays with HEK293T/hACE2 cells showed very similar mean titers: 141 and 178, respectively. ND50 titers positively correlated with plasma IgG targeting SARS-CoV-2 spike and RBD ( r = 0.63–0.89), but moderately correlated with nucleoprotein IgG ( r = 0.46–0.73). ND80 GMTs mirrored ND50 data and showed similar correlation between assays and with IgG concentrations. The VSV-pseudovirus assay and LV-pseudovirus assay with HEK293T/hACE2 cells in low and high-throughput versions were calibrated against the WHO SARS-CoV-2 IgG standard. High concordance between the outcomes of cell-based assays with live and pseudotyped virions enables valid cross-study comparison using these platforms. 249

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Section: Introductionmentioning

confidence: 99%

Evaluation of Cell-Based and Surrogate SARS-CoV-2 Neutralization Assays

et al. 2021

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“…In recent years, nanobodies with neutralizing toxin activity have been studied for the treatment of bacterial toxins, such as those produced by Clostridium difficile , Bacillus anthracis , ricin and anthrax. These accomplishments show that nanobodies represent an alternative anti-infection therapeutic opportunity against bacterial and viral outbreaks ( 126 , 127 ) ( Table 4 ).…”

Section: Nanobody Applications In Infectious Diseasesmentioning

confidence: 99%

“…The receptor-binding domain (RBD) of the spike protein binds to the host cell surface receptor angiotensin-converting enzyme 2 (ACE2). Several anti-spike/anti-RBD neutralizing antibodies have been isolated from both patients and by in vitro selection, some of them have entered clinical trials and cocktails of ligands binding to different epitopes have been proposed to overcome resistance due to the virus mutations ( 127 , 166 ). Multispecific antibody fragments are an alternative solution to prevent mutation-dependent resistance, as it has been already summarized in recent reviews ( 34 , 127 , 167 ).…”

Section: Nanobody Applications In Infectious Diseasesmentioning

confidence: 99%

“…Several anti-spike/anti-RBD neutralizing antibodies have been isolated from both patients and by in vitro selection, some of them have entered clinical trials and cocktails of ligands binding to different epitopes have been proposed to overcome resistance due to the virus mutations ( 127 , 166 ). Multispecific antibody fragments are an alternative solution to prevent mutation-dependent resistance, as it has been already summarized in recent reviews ( 34 , 127 , 167 ). Since the research on anti-SARS-CoV-2 is particularly active and new publications appear constantly, here we report only those relevant to the subject of the present review and published in the first 2021 quarter.…”

Section: Nanobody Applications In Infectious Diseasesmentioning

confidence: 99%

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Research Progress and Applications of Multivalent, Multispecific and Modified Nanobodies for Disease Treatment

et al. 2022

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Recombinant antibodies such as nanobodies are progressively demonstrating to be a valid alternative to conventional monoclonal antibodies also for clinical applications. Furthermore, they do not solely represent a substitute for monoclonal antibodies but their unique features allow expanding the applications of biotherapeutics and changes the pattern of disease treatment. Nanobodies possess the double advantage of being small and simple to engineer. This combination has promoted extremely diversified approaches to design nanobody-based constructs suitable for particular applications. Both the format geometry possibilities and the functionalization strategies have been widely explored to provide macromolecules with better efficacy with respect to single nanobodies or their combination. Nanobody multimers and nanobody-derived reagents were developed to image and contrast several cancer diseases and have shown their effectiveness in animal models. Their capacity to block more independent signaling pathways simultaneously is considered a critical advantage to avoid tumor resistance, whereas the mass of these multimeric compounds still remains significantly smaller than that of an IgG, enabling deeper penetration in solid tumors. When applied to CAR-T cell therapy, nanobodies can effectively improve the specificity by targeting multiple epitopes and consequently reduce the side effects. This represents a great potential in treating malignant lymphomas, acute myeloid leukemia, acute lymphoblastic leukemia, multiple myeloma and solid tumors. Apart from cancer treatment, multispecific drugs and imaging reagents built with nanobody blocks have demonstrated their value also for detecting and tackling neurodegenerative, autoimmune, metabolic, and infectious diseases and as antidotes for toxins. In particular, multi-paratopic nanobody-based constructs have been developed recently as drugs for passive immunization against SARS-CoV-2 with the goal of impairing variant survival due to resistance to antibodies targeting single epitopes. Given the enormous research activity in the field, it can be expected that more and more multimeric nanobody molecules will undergo late clinical trials in the next future.Systematic Review Registration

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“…SARS-CoV-2 entry into the host cell is primarily driven by the receptor-binding domain (RBD) of Spike glycoprotein S that forms a homotrimer able to interact with the host cell receptor angiotensin-converting enzyme 2 (ACE2) [ [2] , [3] , [4] , [5] ]. Because of its role, RBD is also the major target of neutralizing antibodies [ [6] , [7] , [8] ], both natural and recombinant [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Expression, purification and characterization of SARS-CoV-2 spike RBD in ExpiCHO cells

March

Terdoslavich

Polez

et al. 2022

Protein Expression and Purification

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Reliable diagnosis is critical to identify infections of SARS-CoV-2 as well as to evaluate the immune response to virus and vaccines. Consequently, it becomes crucial the isolation of sensitive antibodies to use as immunocapture elements of diagnostic tools. The final bottleneck to achieve these results is the availability of enough antigen of good quality. We have established a robust pipeline for the production of recombinant, functional SARS-CoV-2 Spike receptor binding domain (RBD) at high yield and low cost in culture flasks. RBD was expressed in transiently transfected ExpiCHO cells at 32 °C and 5% CO 2 and purified up to 40 mg/L. The progressive protein accumulation in the culture medium was monitored with an immunobinding assay in order to identify the optimal collection time. Successively, a two-step chromatographic protocol enabled its selective purification in the monomeric state. RBD quality assessment was positively evaluated by SDS-PAGE, Western Blotting and Mass Spectrometry, while Bio-Layer Interferometry, flow cytometer and ELISA tests confirmed its functionality. This effective protocol for the RBD production in transient eukaryotic system can be immediately extended to the production of RBD mutants.

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Coronavirus disease 2019 and the revival of passive immunization: Antibody therapy for inhibiting severe acute respiratory syndrome coronavirus 2 and preventing host cell infection: IUPHAR review 31

Cited by 11 publications

References 125 publications

Evaluation of Cell-Based and Surrogate SARS-CoV-2 Neutralization Assays

Evaluation of Cell-Based and Surrogate SARS-CoV-2 Neutralization Assays

Research Progress and Applications of Multivalent, Multispecific and Modified Nanobodies for Disease Treatment

Expression, purification and characterization of SARS-CoV-2 spike RBD in ExpiCHO cells

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