scholarly journals Sensitivity of SARS-CoV-2 Variants to Neutralization by Convalescent Sera and a VH3-30 Monoclonal Antibody

2021 ◽  
Vol 12 ◽  
Author(s):  
Shuai Yue ◽  
Zhirong Li ◽  
Yao Lin ◽  
Yang Yang ◽  
Mengqi Yuan ◽  
...  
Keyword(s):  
South Africa ◽  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Binding Activity ◽  
Wild Type ◽  
The Past ◽  
Global Pandemic ◽  
Neutralizing Capacity ◽  
Novel Coronavirus ◽  
Medical Countermeasures

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of novel coronavirus disease (COVID-19). Though vaccines and neutralizing monoclonal antibodies (mAbs) have been developed to fight COVID-19 in the past year, one major concern is the emergence of SARS-CoV-2 variants of concern (VOCs). Indeed, SARS-CoV-2 VOCs such as B.1.1.7 (UK), B.1.351 (South Africa), P.1 (Brazil), and B.1.617.1 (India) now dominate the pandemic. Herein, we found that binding activity and neutralizing capacity of sera collected from convalescent patients in early 2020 for SARS-CoV-2 VOCs, but not non-VOC variants, were severely blunted. Furthermore, we observed evasion of SARS-CoV-2 VOCs from a VH3-30 mAb 32D4, which was proved to exhibit highly potential neutralization against wild-type (WT) SARS-CoV-2. Thus, these results indicated that SARS-CoV-2 VOCs might be able to spread in convalescent patients and even harbor resistance to medical countermeasures. New interventions against these SARS-CoV-2 VOCs are urgently needed.

A Dictyostelium mutant with severe defects in alpha-actinin: its characterization using cDNA probes and monoclonal antibodies

1988 ◽  
Vol 90 (1) ◽  
pp. 59-71
Author(s):  
M. Schleicher ◽  
A. Noegel ◽  
T. Schwarz ◽  
E. Wallraff ◽  
M. Brink ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Polypeptide Chain ◽  
Mutant Cell ◽  
Polyacrylamide Gel Electrophoresis ◽  
Cell Extract ◽  
Binding Activity ◽  
Partial Purification ◽  
Wild Type ◽  
Coding Region ◽  
In The Wild

Cells of a Dictyostelium discoideum mutant deficient in binding a monoclonal antibody to alpha-actinin have previously been shown to grow and develop similarly to the wild type and to exert unimpaired chemotaxis as well as patching and capping of membrane proteins. Here we show that the normal 3.0 kb message for alpha-actinin is replaced in the mutant by two RNA species of approximately 3.1 and 2.8 kb. The 3.1 kb RNA was recognized by DNA fragments from all parts of the coding region, while the 2.8 kb RNA hybridized to all but a 3′-terminal fragment. Proteins synthesized in the mutant were analysed using four monoclonal antibodies that in the wild type specifically recognize the 95 × 10(3) Mr polypeptide of alpha-actinin. Cleavage mapping indicated that the binding sites of these antibodies are distributed over a region comprising more than half of the alpha-actinin polypeptide chain. In the mutant, three of the antibodies faintly labelled two polypeptides of 95 × 10(3) Mr and 88 × 10(3) Mr; the fourth antibody, which binds closest to one end of the polypeptide chain, faintly labelled the 95 × 10(3) Mr polypeptide only. The 88 × 10(3) Mr polypeptide most probably lacks the C-terminal portion of alpha-actinin. The binding of an antibody that recognized both polypeptides was quantified by a radio-immuno competition assay using wild-type alpha-actinin as a reference. In a mutant cell extract containing total soluble proteins the antibody binding activity was decreased to 1.1% when compared with wild-type extract. After their partial purification and SDS-polyacrylamide gel electrophoresis the mutant 95 × 10(3) Mr and 88 × 10(3) Mr polypeptides were barely detectable as Coomassie Blue-stained bands, indicating that in the mutant not only certain epitopes of alpha-actinin were altered but the entire molecule is almost completely lacking. When the fitness of mutant cells relative to wild type was determined during growth in nutrient medium, a slight disadvantage for the mutant was indicated, by finding selection coefficients between 0.03 and 0.05.

Distinction of cnxH cofactor gene-specified protomers with monoclonal antibodies to Aspergillus nitrate reductase

1988 ◽  
Vol 34 (1) ◽  
pp. 68-72 ◽  
Author(s):  
R. J. Downey ◽  
P. A. South
Keyword(s):  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Nitrate Reductase ◽  
Aspergillus Nidulans ◽  
Structural Gene ◽  
Molybdenum Cofactor ◽  
Native Enzyme ◽  
Wild Type ◽  
Dimeric Form

The nitrate reductase (NADPH) (EC 1.6.6.3) from Aspergillus nidulans is influenced directly by mutations in the structural gene (niaD) for the major subunit of the enzyme and indirectly by mutation in any of several molybdenum cofactor loci (cnx). The cnxE-14 and the cnxH-3 mutants have been noted to contain the enzyme in two distinct forms following induction with nitrate. With the cnxH-3 as a prototype cnxH mutant, 10 other cnxH were found to be devoid of the assembled (dimeric) form of the enzyme. Two monoclonal antibodies specific for the native enzyme of the wild type (biA-1) recognized an epitope on the enzyme from the cnxE-14 and cnxH-3 mutants that was common to both and another that was unique to the cnxH gene specified protomer. Another monoclonal antibody recognized an epitope that occurs only in the assembled dimeric form of the enzyme from the wild type or the cnxE-14 mutant. The experiments further substantiate the cnxH phenotype as one involving unassembled protomers of the nitrate reductase in Aspergillus.

scholarly journals SARS-CoV-2 variants resist antibody neutralization and broaden host ACE2 usage

2021 ◽  
Author(s):  
Ruoke Wang ◽  
Qi Zhang ◽  
Jiwan Ge ◽  
Wenlin Ren ◽  
Rui Zhang ◽  
...  
Keyword(s):  
South Africa ◽  
Monoclonal Antibodies ◽  
Molecular Basis ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Antibody Neutralization ◽  
Vaccine Protection ◽  
Antigenic Sites ◽  
Global Pandemic ◽  
Crystal Structural

AbstractNew SARS-CoV-2 variants continue to emerge from the current global pandemic, some of which can replicate faster and with greater transmissibility and pathogenicity. In particular, UK501Y.V1 identified in UK, SA501Y.V2 in South Africa, and BR501Y.V3 in Brazil are raising serious concerns as they spread quickly and contain spike protein mutations that may facilitate escape from current antibody therapies and vaccine protection. Here, we constructed a panel of 28 SARS-CoV-2 pseudoviruses bearing single or combined mutations found in the spike protein of these three variants, as well as additional nine mutations that within or close by the major antigenic sites in the spike protein identified in the GISAID database. These pseudoviruses were tested against a panel of monoclonal antibodies (mAbs), including some approved for emergency use to treat SARS-CoV-2 infection, and convalescent patient plasma collected early in the pandemic. SA501Y.V2 pseudovirus was the most resistant, in magnitude and breadth, against mAbs and convalescent plasma, followed by BR501Y.V3, and then UK501Y.V1. This resistance hierarchy corresponds with Y144del and 242-244del mutations in the N-terminal domain as well as K417N/T, E484K and N501Y mutations in the receptor binding domain (RBD). Crystal structural analysis of RBD carrying triple K417N-E484K-N501Y mutations found in SA501Y.V2 bound with mAb P2C-1F11 revealed a molecular basis for antibody neutralization and escape. SA501Y.V2 and BR501Y.V3 also acquired substantial ability to use mouse and mink ACE2 for entry. Taken together, our results clearly demonstrate major antigenic shifts and potentially broadening the host range of SA501Y.V2 and BR501Y.V3, which pose serious challenges to our current antibody therapies and vaccine protection.

COVID-19 and Employment Law in South Africa: Comparative Perspectives on Selected Themes

2021 ◽  
Vol 33 (1) ◽  
pp. 25-55
Author(s):  
Lonias Ndlovu ◽  
Clarence Itumeleng Tshoose
Keyword(s):  
South Africa ◽  
Working Hours ◽  
Employment Law ◽  
Working Environment ◽  
The Novel ◽  
Employment Contracts ◽  
Public Health Emergencies ◽  
Global Pandemic ◽  
Novel Coronavirus ◽  
Comparative Content

Public health emergencies such as the novel coronavirus (COVID-19), which was elevated to a global pandemic, usually have severe implications for people in various spheres of life. For example, people’s employment and social welfare are affected. In this paper, the authors explore the possible implications of COVID-19 on the rights of employers and employees in South Africa. The issues that need to be considered include leave when employees elect to stay at home as a precautionary measure against contracting the coronavirus at work, the enforcement of employment contracts, employment security, workplace discipline, working hours, absenteeism, and the employer’s duty to provide the employees with a safe working environment. Using a doctrinal legal research method, the article provides an analysis of the applicable laws and cases from South Africa and related jurisdictions. The comparative content, analysis of legislation, case law, and sector-specific guidelines show that COVID-19 has and will continue to have a significant impact on the employment laws as reflected in different jurisdictions. Although employment law is generally jurisdiction-specific, there are many commonalities in the laws of different countries, both on the African continent and globally. It is also important to note that the existing employment laws need to be adjusted in order to accommodate the effects of the pandemic. For example, South Africa can draw valuable lessons from other jurisdictions on how to deal with employment matters during a pandemic, and therefore COVID-19 presents the country with an opportunity to develop both its employment laws and the common law.

scholarly journals Epitope Switching as a Novel Escape Mechanism of HIV to CCR5 Monoclonal Antibodies

2010 ◽  
Vol 54 (2) ◽  
pp. 734-741 ◽  
Author(s):  
Andreas Jekle ◽  
Milloni Chhabra ◽  
Adriane Lochner ◽  
Sonja Meier ◽  
Eugene Chow ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Resistant Virus ◽  
Extracellular Loop ◽  
Wild Type ◽  
Hiv Resistance ◽  
Ccr5 Receptor ◽  
N Terminus ◽  
Loop 2 ◽  
Virus Strains

ABSTRACT In passaging experiments, we isolated HIV strains resistant to MAb3952, a chemokine (C-C motif) receptor 5 (CCR5) monoclonal antibody (MAb) that binds to the second extracellular domain (extracellular loop 2 [ECL-2]) of CCR5. MAb3952-resistant viruses remain CCR5-tropic and are cross-resistant to a second ECL-2-specific antibody. Surprisingly, MAb3952-resistant viruses were more susceptible to RoAb13, a CCR5 antibody binding to the N terminus of CCR5. Using CCR5 receptor mutants, we show that MAb3952-resistant virus strains preferentially use the N terminus of CCR5, while the wild-type viruses preferentially use ECL-2. We propose this switch in the CCR5 binding site as a novel mechanism of HIV resistance.

scholarly journals Rapid isolation and profiling of a diverse panel of human monoclonal antibodies targeting the SARS-CoV-2 spike protein

2020 ◽  
Author(s):  
Seth J. Zost ◽  
Pavlo Gilchuk ◽  
Rita E. Chen ◽  
James Brett Case ◽  
Joseph X. Reidy ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Cross Reactivity ◽  
The Novel ◽  
Receptor Binding Domain ◽  
Human Monoclonal Antibodies ◽  
S Protein ◽  
Global Pandemic ◽  
Antibody Discovery ◽  
Novel Coronavirus ◽  
Rapid Antibody

Antibodies are a principal determinant of immunity for most RNA viruses and have promise to reduce infection or disease during major epidemics. The novel coronavirus SARS-CoV-2 has caused a global pandemic with millions of infections and hundreds of thousands of deaths to date1,2. In response, we used a rapid antibody discovery platform to isolate hundreds of human monoclonal antibodies (mAbs) against the SARS-CoV-2 spike (S) protein. We stratify these mAbs into five major classes based on their reactivity to subdomains of S protein as well as their cross-reactivity to SARS-CoV. Many of these mAbs inhibit infection of authentic SARS-CoV-2 virus, with most neutralizing mAbs recognizing the receptor-binding domain (RBD) of S. This work defines sites of vulnerability on SARS-CoV-2 S and demonstrates the speed and robustness of new antibody discovery methodologies.

scholarly journals An Unusual Etiology of Graves’ Disease: Alemtuzumab

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A921-A922
Author(s):  
Ada Marie Santiago Carrion ◽  
Yanerys Agosto-Vargas
Keyword(s):  
Multiple Sclerosis ◽  
Monoclonal Antibody ◽  
Cell Death ◽  
Monoclonal Antibodies ◽  
Programmed Cell Death ◽  
Graves Disease ◽  
The Past ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Abstract Cluster of differentiation 52 (CD-52) is a glycoprotein expressed on the surface of most lymphocytes and it is the most prevalent marker in T cells, B cells, natural killers and monocytes. Alemtuzumab, a CD-52 monoclonal antibody, is one of the initial therapies approved for patients with relapsing-remitting multiple sclerosis. It acts by inducing rapid and prolonged depletion of lymphocytes with a consequent immunosuppression. Although not clearly understood, Alemtuzumab has been associated with the development of autoantibodies. These have been reported to cause thyroid injury resulting in 10-15% incidence of new-onset Graves’ disease. This is the case of a 38 year-old man with medical history of relapsing-remitting multiple sclerosis who came to the Endocrinology clinic to establish care due to abnormal thyroid function tests. Patient has received Alemtuzumab since the past two years. Three months prior to arrival, he was found with weight loss, hyperdefecation and tremors by his Neurologist. Patient was found with suppressed TSH for which Methimazole was commenced. Thyroid ultrasound showed normal size and homogenous right and left thyroid lobes, and no evidence of cystic or solid masses. Thyroid stimulating immunoglobulins were found elevated which correlated with Graves’ disease. Moreover, thyroid scintigraphy showed 34% radioiodine uptake at 24 hours indicating de novo synthesis of thyroid hormone in this patient with hyperthyroidism. As Alemtuzumab was identified as a precipitating cause of Graves’ disease, therapy was discontinued and plasmapheresis will be given for the treatment of relapsing-remitting multiple sclerosis. Monoclonal antibody use has increased since the past decades. It has been well described in literature that monoclonal antibodies against programmed cell death receptor 1 (PD-1) and programmed cell death ligand 1 (PD-L1) may cause autoimmune thyroid disease. Nonetheless, it is important to recognize that other monoclonal antibodies may have similar adverse effects. Alemtuzumab is a monoclonal antibody and antineoplastic agent used for relapsing multiple sclerosis, some hematologic malignancies, and as an induction agent for solid organ transplantation. Its main effects include autoimmunity with thyroid being one of the most described targets. In these patients, expert clinicians should recognize the possibility of thyroid disease for prompt treatment which will improve quality of life.

The efficacy of antiepidermal growth factor receptor monoclonal antibodies for patients with KRAS G13D mutations and chemorefractory metastatic colorectal cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 527-527
Author(s):  
Kohei Akiyoshi ◽  
Yasuhide Yamada ◽  
Naoki Takahashi ◽  
Yoshitaka Honma ◽  
Satoru Iwasa ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Growth Factor ◽  
Metastatic Colorectal Cancer ◽  
Growth Factor Receptor ◽  
Cancer Center ◽  
Wild Type ◽  
Duration Of Treatment ◽  
Kras Mutations

527 Background: The treatment benefits of epidermal growth factor receptor (EGFR) monoclonal antibodies for patients with KRAS mutations have not been demonstrated. However, some studies have suggested that all KRAS mutations are not equivalent, and that KRAS G13D mutations might have some survival benefit. Methods: We retrospectively analyzed the efficacy and toxicity of treatment with EGFR monoclonal antibody in 8 patients with KRAS G13D mutations and 5-FU/oxaliplatin/irinotecan (CPT) refractory metastatic colorectal cancer compared with 94 KRAS wild type patients at the National Cancer Center Hospital. Results: Eight patients with KRAS G13D mutations were treated with anti-EGFR monoclonal antibodies between July, 2009 and July, 2011. The median age was 66 (42-70); male/female 6/2; PS was 0/1/2, 2/5/1; treatment regimen was cetuximab/ cetuximab+CPT/ panitumumab+CPT, 2/5/1. Response rate (RR) was 12.5% and disease control rate (DCR) was 50.0% with 1 PR, 3 SD, and 4 PD. The PR case treated with cetuximab+CPT showed marked regression of tumor and long duration of treatment (9 months). The progression free survival (PFS) of 2 SD cases was 4.2 and 3.9 months. The other SD case is now on treatment. The median PFS of the 8 patients was 2.1 months (95% confidence interval [CI]: 0.0-5.2). The median overall survival (OS) has not been reached. Grade 3/4 toxicities included 1 hypomagnesemia G4 and 1 rash acneiform G3. Meanwhile, 94 KRAS wild type patients treated with anti EGFR monoclonal antibodies had an RR of 22.3% and DCR was 66.0% with 21 PR, 41 SD, 30 PD, and 2 NE. PFS was 5.6 months (95% CI: 4.9-6.3) and OS was 8.6 months (95% CI: 6.5-10.7). Conclusions: In this analysis, we identified one PR to anti-EGFR monoclonal antibody in a patient with KRAS G13D mutation and chemo-refractory metastatic colorectal cancer. However, we were unable to demonstrate equivalent efficacy in patients with KRAS G13D mutations and KRAS wild type patients. Further studies are needed to evaluate the efficacy and prognosis for this treatment.

scholarly journals Establishing a Distribution Network for COVID-19 Monoclonal Antibody Therapy Across a Large Health System During a Global Pandemic

2021 ◽  
Author(s):  
J Ryan Bariola ◽  
Erin K McCreary ◽  
Tina Khadem ◽  
Graham M Snyder ◽  
Richard J Wadas ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Health System ◽  
Distribution Network ◽  
Antibody Therapy ◽  
Lessons Learned ◽  
Monoclonal Antibody Therapy ◽  
Global Pandemic

Abstract Emergency authorized COVID-19 neutralizing monoclonal antibodies can aid outpatients with mild to moderate COVID-19 infection. Many report barriers to adequate distribution and uptake. We present our model for distribution in a large health system as well as early lessons learned.

scholarly journals Post-apartheid South Africa’s exacerbated inequality and the Covid-19 pandemic: intersectionality and the politics of power

2021 ◽  
pp. 68-78
Author(s):  
Juliet Eileen Joseph
Keyword(s):  
South Africa ◽  
Social Relations ◽  
Research Approach ◽  
Protest Movements ◽  
The Past ◽  
Global Pandemic ◽  
Kwazulu Natal ◽  
Race Ethnicity ◽  
Intersectional Theory ◽  
Apartheid Regime

Over the past fifteen years there has been an increase in the number of protest movements globally. In recent years and amid the global pandemic there have been hundreds of protests and demonstrations in South Africa. Consequently, in comparison to other parts of the globe, such protest action in South Africa is high. As a result, stable governance in the region has been impacted. Notably, during the resistance years in defiance of the apartheid regime, citizens in South Africa expressed their social discontent against exclusion and marginalisation through identities as radical and intersectional – this was also articulated in the recent protests that occurred in KwaZulu-Natal and parts of Johannesburg in July 2021. This highlights the relevance of intersectionality within this region. Intersectionality can be seen to refer to the inequalities that exist beyond femininities and masculinities. Intersectional theory explores aspects of discrimination, oppression, exploitation and inequality across identity, gender, race, ethnicity and class. This study uses a qualitative research approach to conceptually analyse intersectional theory. Thereafter the study discusses the relevance of intersectional theory in a post-apartheid context by illustrating intersectionality through the unrest and protests that occurred, following the jailing of former president Jacob Zuma. The findings of the study suggest the need to unpack the legacies of African elitism and social relations, while implementing intersectional reform that promotes greater inclusivity of citizens in the state.

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