scholarly journals Efficacy and safety of a third SARS-CoV-2 vaccination in multiple sclerosis vaccine non-responders

2021 ◽  
Author(s):  
Marton Konig ◽  
Hilde Marie Torgauten ◽  
Marthias Herstad Overas ◽  
Adity Chopra ◽  
Aslaug Rudjord Lorentzen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Side Effects ◽  
Severe Acute Respiratory Syndrome ◽  
Humoral Immunity ◽  
Vaccine Dose ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Efficacy And Safety ◽  
Immunization Registry ◽  
Anti Cd20

Importance: Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to protect against coronavirus disease of 2019 (COVID-19) is recommended for patients with multiple sclerosis (pwMS). However, approximately 80% of all pwMS treated with anti-CD20 therapy (rituximab, ocrelizumab) or fingolimod have low or absent humoral immunity after vaccination with two doses of SARS-CoV-2 mRNA vaccines. The efficacy and safety of a third vaccine dose in this group is largely unknown. Objective: To characterize the humoral immunogenicity and the safety of a third dose of mRNA-COVID-19 vaccine in anti-CD20- or fingolimod-treated pwMS with low or absent humoral immunity (i.e., anti-SARS-CoV-2 IgG <70 arbitrary units (AU) and <5 AU, respectively) after two vaccinations. Design, setting and participants: 130 anti-CD20- or fingolimod-treated pwMS with low or absent humoral immunity despite full vaccination against SARS-CoV-2, received a third dose of SARS-CoV-2 mRNA vaccine. Humoral immunity (i.e., antibody response against SARS-CoV-2) and the frequency and characteristics of side-effects were analyzed in all participants. Exposures: A third vaccine dose against SARS-CoV-2 with BNT162b2- or mRNA-1273-COVID-19 vaccine. Main outcomes and measures: Patient- and treatment-specific variables were acquired using a digital questionnaire, the Norwegian Immunization Registry and hospital journals. Humoral immunity was assessed by measuring SARS-CoV-2 SPIKE receptor-binding domain (RBD) IgG response. Low/absent humoral immunity was assumed in cases of AU<70 after anti-SPIKE protein-based serology 3-5 weeks after revaccination. Results: A third dose of SARS-CoV-2 mRNA vaccine increased anti-SARS-CoV-2 SPIKE RBD IgG levels significantly. The proportion of patients with assumed protective humoral immunity (anti-SARS-CoV-2 SPIKE RBD IgG > 70 AU) were 25% among patients using anti-CD20 therapy and 7% among those treated with fingolimod. No adverse events were registered during the study period. Conclusion and relevance: A third dose of mRNA-COVID-19 vaccine was associated with significantly increased levels of anti-SARS-CoV-2 SPIKE RBD IgG, and hence assumed protective humoral immunity - in anti-CD20- or fingolimod-treated pwMS with low or absent humoral immunity despite full vaccination. The effect of a third vaccine dose was limited and more prominent among those treated with anti-CD20 therapy.

scholarly journals Post-vaccine COVID-19 in patients with multiple sclerosis or neuromyelitis optica

2021 ◽  
pp. 135245852110497
Author(s):  
Edouard Januel ◽  
Jérôme De Seze ◽  
Patrick Vermersch ◽  
Elisabeth Maillart ◽  
Bertrand Bourre ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Neuromyelitis Optica ◽  
Immunoglobulin G ◽  
Vaccine Efficacy ◽  
Case Series ◽  
Vaccine Dose ◽  
Spike Protein ◽  
Biological Study ◽  
Anti Cd20

Introduction: Recent studies suggested that anti-CD20 and fingolimod may be associated with lower anti-spike protein-based immunoglobulin-G response following COVID-19 vaccination. We evaluated if COVID-19 occurred despite vaccination among patients with multiple sclerosis (MS) and neuromyelitis optica (NMO), using the COVISEP registry. Case series: We report 18 cases of COVID-19 after two doses of BNT162b2-vaccination, 13 of which treated with anti-CD20 and four with fingolimod. COVID-19 severity was mild. Discussion: These results reinforce the recommendation for a third COVID-19 vaccine dose among anti-CD20 treated patients and stress the need for a prospective clinical and biological study on COVID-19 vaccine efficacy among MS and NMO patients.

scholarly journals Identification of Common Deletions in the Spike Protein of Severe Acute Respiratory Syndrome Coronavirus 2

2020 ◽  
Vol 94 (17) ◽  
Author(s):  
Zhe Liu ◽  
Huanying Zheng ◽  
Huifang Lin ◽  
Mingyue Li ◽  
Runyu Yuan ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Virus Replication ◽  
Receptor Binding ◽  
Cleavage Site ◽  
Spike Protein ◽  
Clinical Samples ◽  
Receptor Binding Domain ◽  
Flanking Sequence

ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus first identified in December 2019. Notable features that make SARS-CoV-2 distinct from most other previously identified betacoronaviruses include a receptor binding domain and a unique insertion of 12 nucleotides or 4 amino acids (PRRA) at the S1/S2 boundary. In this study, we identified two deletion variants of SARS-CoV-2 that either directly affect the polybasic cleavage site itself (NSPRRAR) or a flanking sequence (QTQTN). These deletions were verified by multiple sequencing methods. In vitro results showed that the deletion of NSPRRAR likely does not affect virus replication in Vero and Vero-E6 cells; however, the deletion of QTQTN may restrict late-phase viral replication. The deletion of QTQTN was detected in 3 of 68 clinical samples and 12 of 24 in vitro-isolated viruses, while the deletion of NSPRRAR was identified in 3 in vitro-isolated viruses. Our data indicate that (i) there may be distinct selection pressures on SARS-CoV-2 replication or infection in vitro and in vivo; (ii) an efficient mechanism for deleting this region from the viral genome may exist, given that the deletion variant is commonly detected after two rounds of cell passage; and (iii) the PRRA insertion, which is unique to SARS-CoV-2, is not fixed during virus replication in vitro. These findings provide information to aid further investigation of SARS-CoV-2 infection mechanisms and a better understanding of the NSPRRAR deletion variant observed here. IMPORTANCE The spike protein determines the infectivity and host range of coronaviruses. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has two unique features in its spike protein, the receptor binding domain and an insertion of 12 nucleotides at the S1/S2 boundary resulting in a furin-like cleavage site. Here, we identified two deletion variants of SARS-CoV-2 that either directly affect the furin-like cleavage site itself (NSPRRAR) or a flanking sequence (QTQTN), and we investigated these deletions in cell isolates and clinical samples. The absence of the polybasic cleavage site in SARS-CoV-2 did not affect virus replication in Vero or Vero-E6 cells. Our data indicate the PRRAR sequence and the flanking QTQTN sequence are not fixed in vitro; thus, there appears to be distinct selection pressures on SARS-CoV-2 sequences in vitro and in vivo. Further investigation of the mechanism of generating these deletion variants and their infectivity in different animal models would improve our understanding of the origin and evolution of this virus.

scholarly journals Neutralizing Monoclonal Antibodies That Target the Spike Receptor Binding Domain Confer Fc Receptor-Independent Protection against SARS-CoV-2 Infection in Syrian Hamsters

mBio ◽  
2021 ◽  
Author(s):  
Wen Su ◽  
Sin Fun Sia ◽  
Aaron J. Schmitz ◽  
Traci L. Bricker ◽  
Tyler N. Starr ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Severe Acute Respiratory Syndrome ◽  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Fc Receptor ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Syrian Hamsters ◽  
Convalescent Phase ◽  
Main Target

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein is the main target for neutralizing antibodies. These antibodies can be elicited through immunization or passively transferred as therapeutics in the form of convalescent-phase sera or monoclonal antibodies (MAbs).

scholarly journals Predictive profiling of SARS-CoV-2 variants by deep mutational learning

2021 ◽  
Author(s):  
Joseph M Taft ◽  
Cedric R Weber ◽  
Beichen Gao ◽  
Roy A Ehling ◽  
Jiami Han ◽  
...  
Keyword(s):  
Machine Learning ◽  
Decision Making ◽  
Severe Acute Respiratory Syndrome ◽  
Sequence Space ◽  
Neutralizing Antibodies ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Primary Target ◽  
Engineering Technology ◽  
Evolutionary Trajectories

The continual evolution of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and the emergence of variants that show resistance to vaccines and neutralizing antibodies threaten to prolong the coronavirus disease 2019 (COVID-19) pandemic. Selection and emergence of SARS-CoV-2 variants are driven in part by mutations within the viral spike protein and in particular the ACE2 receptor-binding domain (RBD), a primary target site for neutralizing antibodies. Here, we develop deep mutational learning (DML), a machine learning-guided protein engineering technology, which is used to interrogate a massive sequence space of combinatorial mutations, representing billions of RBD variants, by accurately predicting their impact on ACE2 binding and antibody escape. A highly diverse landscape of possible SARS-CoV-2 variants is identified that could emerge from a multitude of evolutionary trajectories. DML may be used for predictive profiling on current and prospective variants, including highly mutated variants such as omicron (B.1.1.529), thus supporting decision making for public heath as well as guiding the development of therapeutic antibody treatments and vaccines for COVID-19.

scholarly journals Binding and entering: COVID finds a new home

2021 ◽  
Vol 17 (8) ◽  
pp. e1009857
Author(s):  
Michelle N. Vu ◽  
Vineet D. Menachery
Keyword(s):  
Middle East ◽  
Severe Acute Respiratory Syndrome ◽  
Receptor Binding ◽  
Common Cold ◽  
Binding Domain ◽  
Middle East Respiratory Syndrome ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Protease Cleavage ◽  
Pandemic Virus

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) emerged as a virus with a pathogenicity closer to Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and a transmissibility similar to common cold coronaviruses (CoVs). In this review, we briefly discuss the features of the receptor-binding domain (RBD) and protease cleavage of the SARS-CoV-2 spike protein that enable SARS-CoV-2 to be a pandemic virus.

scholarly journals Synthetic antibodies neutralize SARS-CoV-2 infection of mammalian cells

2020 ◽  
Author(s):  
Shane Miersch ◽  
Mart Ustav ◽  
Zhijie Li ◽  
James B. Case ◽  
Safder Ganaie ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Severe Acute Respiratory Syndrome ◽  
Receptor Binding ◽  
Mammalian Cells ◽  
Rna Viruses ◽  
Large Family ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Highly Pathogenic ◽  
Zoonotic Infections

ABSTRACTCoronaviruses (CoV) are a large family of enveloped, RNA viruses that circulate in mammals and birds. Three highly pathogenic strains have caused zoonotic infections in humans that result in severe respiratory syndromes including the Middle East Respiratory Syndrome CoV (MERS), Severe Acute Respiratory Syndrome CoV (SARS), and the ongoing Coronavirus Disease 2019 (COVID-19) pandemic. Here, we describe a panel of synthetic monoclonal antibodies, built on a human IgG framework, that bind to the spike protein of SARS-CoV-2 (the causative agent of COVID-19), compete for ACE2 binding, and potently inhibit SARS-CoV-2. All antibodies that exhibited neutralization potencies at sub-nanomolar concentrations against SARS-CoV-2/USA/WA1 in Vero E6 cells, also bound to the receptor binding domain (RBD), suggesting competition for the host receptor ACE2. These antibodies represent strong immunotherapeutic candidates for treatment of COVID-19.

Design and Synthesis of De Novo Boomerang Shaped Molecules and their In Silico & SERS-based Interactions with SARS-CoV-2 Spike Protein and ACE2

2021 ◽  
Author(s):  
Amrutham Linet ◽  
Manu M Joseph ◽  
Haritha Mambatta ◽  
Shamna k ◽  
Sunil varughese ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Receptor Binding ◽  
In Silico ◽  
De Novo ◽  
Binding Domain ◽  
Spike Protein ◽  
Epithelial Tissue ◽  
Receptor Binding Domain ◽  
Design And Synthesis ◽  
Recent Outbreak

The recent outbreak of the COVID-19 pandemic is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which infects human epithelial tissue by interaction of the receptor-binding domain of its spike...

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