Purpose: Casirivimab/imdevimab (REGN-COV), a cocktail of neutralizing antibodies against the receptor-binding domain of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, was shown to be an effective treatment and post-exposure prophylaxis measure for coronavirus disease 2019 (COVID-19). We assessed the antibody titers among patients who received REGN-COV with the purpose of evaluating this therapeutic and prophylactic option from the serological point of view.
Methods: We collected serological data of patients with COVID-19 who were treated with REGN-COV 1200 mg (casirivimab 600 mg/imdevimab 600 mg). Antibody titers were assessed within 24 h before and within 48 h after the administration of REGN-COV using ARCHITECT SARS-CoV-2 immunoglobulin (Ig)G (IgGNC), which is against nucleocapsid protein, and ARCHITECT SARS-CoV-2 IgG II Quant (IgGSP), which is against spike protein.
Results: A total of nine patients were evaluated. IgGSP was elevated after REGN-COV administration with a median of 208,370 Arbitrary Units/mL while simultaneous IgGNC remained low. With the simple linear regression model, the IgGSP after the REGN-COV administration was correlated with the reciprocal of ideal body weight.
Conclusion: The high titer of IgGSP supports the clinical benefit of therapeutic and prophylactic use of REGN-COV from the serological point of view.
Heterotypic interactions drive antibody synergy against a malaria vaccine candidate
Understanding mechanisms of antibody synergy is important for vaccine design and antibody cocktail development. Examples of synergy between antibodies are well-documented, but the mechanisms underlying these relationships often remain poorly understood. The leading blood-stage malaria vaccine candidate, CyRPA, is essential for invasion of Plasmodium falciparum into human erythrocytes. Here we present a panel of anti-CyRPA monoclonal antibodies that strongly inhibit parasite growth in in vitro assays.
Structural studies show that growth-inhibitory antibodies bind epitopes on a single face of CyRPA. We also show that pairs of non-competing inhibitory antibodies have strongly synergistic growth-inhibitory activity. These antibodies bind to neighbouring epitopes on CyRPA and form lateral, heterotypic interactions which slow antibody dissociation. We predict that such heterotypic interactions will be a feature of many immune responses. Immunogens which elicit such synergistic antibody mixtures could increase the potency of vaccine-elicited responses to provide robust and long-lived immunity against challenging disease targets.
Development and characterization of functional antibodies targeting NMDA receptors
N-methyl-D-aspartate receptors (NMDARs) are critically involved in basic brain functions and neurodegeneration as well as tumor invasiveness. Targeting specific subtypes of NMDARs with distinct activities has been considered an effective therapeutic strategy for neurological disorders and diseases. However, complete elimination of off-target effects of small chemical compounds has been challenging and thus, there is a need to explore alternative strategies for targeting NMDAR subtypes. Here we report identification of a functional antibody that specifically targets the GluN1-GluN2B NMDAR subtype and allosterically down-regulates ion channel activity as assessed by electrophysiology.
Through biochemical analysis, x-ray crystallography, single-particle electron cryomicroscopy, and molecular dynamics simulations, we show that this inhibitory antibody recognizes the amino terminal domain of the GluN2B subunit and increases the population of the non-active conformational state. The current study demonstrates that antibodies may serve as specific reagents to regulate NMDAR functions for basic research and therapeutic objectives.
Influenza virus infection history shapes antibody responses to influenza vaccination
- Studies of successive vaccination suggest that immunological memory against past influenza viruses may limit responses to vaccines containing current strains. The impact of memory induced by prior infection is rarely considered and is difficult to ascertain, because infections are often subclinical. This study investigated influenza vaccination among adults from the Ha Nam cohort (Vietnam), who were purposefully selected to include 72 with and 28 without documented influenza A(H3N2) infection during the preceding 9 years (Australian New Zealand Clinical Trials Registry 12621000110886).
- The primary outcome was the effect of prior influenza A(H3N2) infection on hemagglutinin-inhibiting antibody responses induced by a locally available influenza vaccine administered in November 2016. Baseline and postvaccination sera were titrated against 40 influenza A(H3N2) strains spanning 1968-2018. At each time point (baseline, day 14 and day 280), geometric mean antibody titers against 2008-2018 strains were higher among participants with recent infection (34 (29-40), 187 (154-227) and 86 (72-103)) than among participants without recent infection (19 (17-22), 91 (64-130) and 38 (30-49)). On days 14 and 280, mean titer rises against 2014-2018 strains were 6.1-fold (5.0- to 7.4-fold) and 2.6-fold (2.2- to 3.1-fold) for participants with recent infection versus 4.8-fold (3.5- to 6.7-fold) and 1.9-fold (1.5- to 2.3-fold) for those without.
- One of 72 vaccinees with recent infection versus 4 of 28 without developed symptomatic A(H3N2) infection in the season after vaccination (P = 0.021). The range of A(H3N2) viruses recognized by vaccine-induced antibodies was associated with the prior infection strain. These results suggest that recall of immunological memory induced by prior infection enhances antibody responses to inactivated influenza vaccine and is important to attain protective antibody titers.
Thyroid-Stimulatory Antibody as a Predictive Factor for Graves’ Disease Relapse
Introduction: Thyroid-stimulatory antibody (TSAb) assays have been recently optimized, potentially allowing to determine thyrotropin receptor antibodies’ (TRAbs) functionality in routine clinical practice. We aimed to determine TSAb’s predictive role of relapse at antithyroid drug (ATD) withdrawal in Graves’ disease (GD).
Methods: Retrospective study of GD patients with stable normal thyroid function under low ATD doses that were proposed for withdrawal. Thyroid function tests and TRAb and TSAb levels were obtained at ATD suspension and every three to six months after that, for a minimum of 16 months. Clinical factors associated with GD relapse, such as age at diagnosis, sex, smoking status, thyroid volume, and presence of orbitopathy, were also evaluated.
Results: Thirty-five patients with GD were included for analysis, with a median follow-up period of 24 months, during which 14 patients (40%) relapsed. Relapse was more common in patients with positive TSAb than patients with negative TSAb at ATD withdrawal (79% vs. 33%, p=0.01). Relapse-free survival was shorter in TSAb-positive patients (p=0.01). There were no differences in relapse rates according to TRAb positivity at ATD withdrawal (42.9% vs. 36.4%, p=0.74). We also did not find any differences in relapse rate regarding age, sex, smoking status, thyroid volume, or presence of Graves’ orbitopathy. On multivariate analysis, only TSAb positivity at ATD withdrawal was independently associated with relapse (hazard ratio [HR] 6.63, 95% confidence interval [CI], 1.30-33.7, p=0.02).
Conclusion: At ATD withdrawal, TSAb-positive patients demonstrated a higher risk for GD relapse. Measuring TSAb before ATD suspension, instead of TRAbs, could become an important tool for the clinical management of these patients.
Oxidative Stress Antibodies Set | 5 antibodies |
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| AS19-4294 | Agrisera AB | each | 1472 EUR |
DNA Monoclonal Antibodies |
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| MBS191417-2x01mg | MyBiosource | 2x0.1mg | 310 EUR |
Lipase Monoclonal Antibodies |
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| MBS191421-4x01mg | MyBiosource | 4x0.1mg | 570 EUR |
Trypsin Monoclonal Antibodies |
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| MBS191422-3x01mg | MyBiosource | 3x0.1mg | 440 EUR |
Amylase Monoclonal Antibodies |
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| MBS191423-3x01mg | MyBiosource | 3x0.1mg | 440 EUR |
Digoxin Monoclonal Antibodies |
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| MBS191461-3x01mg | MyBiosource | 3x0.1mg | 440 EUR |
Phenytoin Monoclonal Antibodies |
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| MBS191449-5x01mg | MyBiosource | 5x0.1mg | 695 EUR |
Quinidine Monoclonal Antibodies |
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| MBS191451-5x01mg | MyBiosource | 5x0.1mg | 695 EUR |
Lidocaine Monoclonal Antibodies |
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| MBS191452-5x01mg | MyBiosource | 5x0.1mg | 695 EUR |
Imipramine Monoclonal Antibodies |
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| MBS191446-3x01mg | MyBiosource | 3x0.1mg | 440 EUR |
Gentamicin Monoclonal Antibodies |
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| MBS191447-2x01mg | MyBiosource | 2x0.1mg | 320 EUR |
Sperm Antibodies ELISA kit |
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| 55R-IB79154 | Fitzgerald | 96 wells | 353 EUR |
Sperm Antibodies ELISA kit |
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| 55R-IB79155 | Fitzgerald | 96 wells | 388 EUR |
Sperm Antibodies ELISA kit |
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| 55R-IB79156 | Fitzgerald | 96 wells | 331 EUR |
Chymotrypsin Monoclonal Antibodies |
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| MBS191424-4x01mg | MyBiosource | 4x0.1mg | 585 EUR |
Disopyramide Monoclonal Antibodies |
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| MBS191445-4x01mg | MyBiosource | 4x0.1mg | 570 EUR |
Theophylline Monoclonal Antibodies |
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| MBS191448-9x01mg | MyBiosource | 9x0.1mg | 1205 EUR |
Procainamide Monoclonal Antibodies |
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| MBS191453-7x01mg | MyBiosource | 7x0.1mg | 955 EUR |
SULT1E1 RabbitPolyclonal Antibodies |
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| 29221 | SAB | 100ul | 439 EUR |
Phenobarbital Monoclonal Antibodies |
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| MBS191450-5x01mg | MyBiosource | 5x0.1mg | 695 EUR |
Amitriptyline Monoclonal Antibodies |
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| MBS191462-2x01mg | MyBiosource | 2x0.1mg | 310 EUR |
E Coli Monoclonal Antibodies |
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| MBS191440-5x01mg | MyBiosource | 5x0.1mg | 695 EUR |
CA-125 Monoclonal Antibodies |
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| MBS190629-01mg | MyBiosource | 0.1mg | 370 EUR |
CA-125 Monoclonal Antibodies |
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| MBS190629-5x01mg | MyBiosource | 5x0.1mg | 1650 EUR |
CA-125 Monoclonal Antibodies |
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| MBS190630-01mg | MyBiosource | 0.1mg | 370 EUR |
CA-125 Monoclonal Antibodies |
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| MBS190630-5x01mg | MyBiosource | 5x0.1mg | 1650 EUR |
[A monoclonal antibody-based icELISA for puerarin]
Puerarin was conjugated with bovine serum albumin(BSA) and ovalbumin(OVA) by periodate oxidation to serve as the immunogen and coating antigen, respectively. BALB/c mice were immunized with puerarin-BSA according to the routine immunization procedure, and the titer and specificity of serum were detected after three immunization. After booster immunization, mouse spleen lymphocytes were fused with mouse myeloma cells, and 24 hybridoma cell lines of the monoclonal antibodies against puerarin were screened by monoclonal antibody screening technique. Ascites was prepared and purified.
The cross-reactivity of monoclonal antibody(mAb) M1 with 4′-methoxy puerarin, daidzin, puerarin-6″-O-xyloside, daidzein, mirificin, 3′-methoxy puerarin, and 3′-hydroxy puerarin was 239.84%, 112.18%, 67.89%, 58.28%, 22.37%, 0.40%, and 0.20%, respectively, and those with other analogs such as baicalein and baicalin were all less than 0.10%. The IC_(50) and the working range of the indirect competitive enzyme-linked immunosorbent assay(icELISA) for puerarin were 44.80 ng·mL~(-1) and 8.20-292.30 ng·mL~(-1), respectively. The average recovery was 91.95%-98.20% with an RSD in the range of 0.70%-2.60%. The content of puerarin in different Puerariae Lobatae Radix samples was determined with icELISA and validated by UPLC-MS. The correlation between data obtained from icELISA and UPLC-MS was 0.999 0, indicating that icELISA is suitable for the rapid detection of puerarin in Puerariae Lobatae Radix samples.