scholarly journals A potent broad-spectrum protective human monoclonal antibody crosslinking two haemagglutinin monomers of influenza A virus

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Ying Wu ◽  
MyungSam Cho ◽  
David Shore ◽  
Manki Song ◽  
JungAh Choi ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Influenza A Virus ◽  
Broad Spectrum ◽  
Influenza A ◽  
Human Monoclonal Antibody

scholarly journals In VitroAssessment of the Immunological Significance of a Human Monoclonal Antibody Directed to the Influenza A Virus Nucleoprotein

2013 ◽  
Vol 20 (8) ◽  
pp. 1333-1337 ◽  
Author(s):  
Rogier Bodewes ◽  
Martina M. Geelhoed-Mieras ◽  
Jens Wrammert ◽  
Rafi Ahmed ◽  
Patrick C. Wilson ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Influenza A Virus ◽  
Influenza A ◽  
Viral Antigen ◽  
Human Monoclonal Antibody ◽  
Cell Cytotoxicity ◽  
Influenza A Viruses ◽  
Dependent Cell ◽  
Infected Cells

ABSTRACTInfluenza A viruses cause annual epidemics and occasionally pandemics. Antibodies directed to the conserved viral nucleoprotein (NP) may play a role in immunity against various influenza A virus subtypes. Here, we assessed the immunological significance of a human monoclonal antibody directed to NPin vitro. This antibody bound to virus-infected cells but did not display virus-neutralizing activity, complement-dependent cell cytotoxicity, or opsonization of viral antigen for improved antigen presentation to CD8+T cells by dendritic cells.

Characterization of a fully human monoclonal antibody against extracellular domain of matrix protein 2 of influenza A virus

2011 ◽  
Vol 91 (3) ◽  
pp. 283-287 ◽  
Author(s):  
Tatsuhiko Ozawa ◽  
Aishun Jin ◽  
Kazuto Tajiri ◽  
Masaya Takemoto ◽  
Tomoko Okuda ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Influenza A Virus ◽  
Influenza A ◽  
Matrix Protein ◽  
Human Monoclonal Antibody ◽  
Extracellular Domain

Therapeutic potential of a fully human monoclonal antibody against influenza A virus M2 protein

2008 ◽  
Vol 80 (2) ◽  
pp. 168-177 ◽  
Author(s):  
R WANG ◽  
A SONG ◽  
J LEVIN ◽  
D DENNIS ◽  
N ZHANG ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Influenza A Virus ◽  
Influenza A ◽  
Therapeutic Potential ◽  
Human Monoclonal Antibody ◽  
M2 Protein

scholarly journals Phase 2 Randomized Trial of the Safety and Efficacy of MHAA4549A, a Broadly Neutralizing Monoclonal Antibody, in a Human Influenza A Virus Challenge Model

2017 ◽  
Vol 61 (11) ◽  
Author(s):  
Jacqueline M. McBride ◽  
Jeremy J. Lim ◽  
Tracy Burgess ◽  
Rong Deng ◽  
Michael A. Derby ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Viral Load ◽  
Influenza A Virus ◽  
Influenza A ◽  
Human Monoclonal Antibody ◽  
Area Under The Curve ◽  
Inflammatory Biomarkers ◽  
Double Blind ◽  
Safety And Efficacy ◽  
Virus Challenge

ABSTRACT MHAA4549A, a human monoclonal antibody targeting the hemagglutinin stalk region of influenza A virus (IAV), is being developed as a therapeutic for patients hospitalized with severe IAV infection. The safety and efficacy of MHAA4549A were assessed in a randomized, double-blind, placebo-controlled, dose-ranging study in a human IAV challenge model. One hundred healthy volunteers were inoculated with A/Wisconsin/67/2005 (H3N2) IAV and, 24 to 36 h later, administered a single intravenous dose of either placebo, MHAA4549A (400, 1,200, or 3,600 mg), or a standard oral dose of oseltamivir. Subjects were assessed for safety, pharmacokinetics (PK), and immunogenicity. The intent-to-treat-infected (ITTI) population was assessed for changes in viral load, influenza symptoms, and inflammatory biomarkers. MHAA4549A was well tolerated in all IAV challenge subjects. The 3,600-mg dose of MHAA4549A significantly reduced the viral burden relative to that of the placebo as determined by the area under the curve (AUC) of nasopharyngeal virus infection, quantified using quantitative PCR (98%) and 50% tissue culture infective dose (TCID50) (100%) assays. Peak viral load, duration of viral shedding, influenza symptom scores, mucus weight, and inflammatory biomarkers were also reduced. Serum PK was linear with a half-life of ∼23 days. No MHAA4549A-treated subjects developed anti-drug antibodies. In conclusion, MHAA4549A was well tolerated and demonstrated statistically significant and substantial antiviral activity in an IAV challenge model. (This study has been registered at ClinicalTrials.gov under identifier NCT01980966.)

scholarly journals Preclinical pharmacokinetics of MHAA4549A, a human monoclonal antibody to influenza A virus, and the prediction of its efficacious clinical dose for the treatment of patients hospitalized with influenza A

mAbs ◽  
2016 ◽  
Vol 8 (5) ◽  
pp. 991-997 ◽  
Author(s):  
Priyanka Gupta ◽  
Amrita V. Kamath ◽  
Summer Park ◽  
Henry Chiu ◽  
Jeff Lutman ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Influenza A Virus ◽  
Influenza A ◽  
Human Monoclonal Antibody ◽  
Preclinical Pharmacokinetics ◽  
Clinical Dose

scholarly journals Thapsigargin Is a Broad-Spectrum Inhibitor of Major Human Respiratory Viruses: Coronavirus, Respiratory Syncytial Virus and Influenza A Virus

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 234
Author(s):  
Sarah Al-Beltagi ◽  
Cristian Alexandru Preda ◽  
Leah V. Goulding ◽  
Joe James ◽  
Juan Pu ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Respiratory Syncytial Virus ◽  
Influenza A Virus ◽  
Broad Spectrum ◽  
Influenza A ◽  
Respiratory Viruses ◽  
Influenza Viruses ◽  
Virus Challenge ◽  
2009 H1n1 ◽  
Syncytial Virus

The long-term control strategy of SARS-CoV-2 and other major respiratory viruses needs to include antivirals to treat acute infections, in addition to the judicious use of effective vaccines. Whilst COVID-19 vaccines are being rolled out for mass vaccination, the modest number of antivirals in use or development for any disease bears testament to the challenges of antiviral development. We recently showed that non-cytotoxic levels of thapsigargin (TG), an inhibitor of the sarcoplasmic/endoplasmic reticulum (ER) Ca2+ ATPase pump, induces a potent host innate immune antiviral response that blocks influenza A virus replication. Here we show that TG is also highly effective in blocking the replication of respiratory syncytial virus (RSV), common cold coronavirus OC43, SARS-CoV-2 and influenza A virus in immortalized or primary human cells. TG’s antiviral performance was significantly better than remdesivir and ribavirin in their respective inhibition of OC43 and RSV. Notably, TG was just as inhibitory to coronaviruses (OC43 and SARS-CoV-2) and influenza viruses (USSR H1N1 and pdm 2009 H1N1) in separate infections as in co-infections. Post-infection oral gavage of acid-stable TG protected mice against a lethal influenza virus challenge. Together with its ability to inhibit the different viruses before or during active infection, and with an antiviral duration of at least 48 h post-TG exposure, we propose that TG (or its derivatives) is a promising broad-spectrum inhibitor against SARS-CoV-2, OC43, RSV and influenza virus.

scholarly journals Biochemical and structural characterization of the interface mediating interaction between the influenza A virus non-structural protein-1 and a monoclonal antibody

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Jianping Wu ◽  
Chee-Keng Mok ◽  
Vincent Tak Kwong Chow ◽  
Y. Adam Yuan ◽  
Yee-Joo Tan
Keyword(s):  
Monoclonal Antibody ◽  
Influenza A Virus ◽  
Structural Characterization ◽  
Influenza A ◽  
Structural Protein

Pharmacokinetics of MHAA4549A, an Anti-Influenza A Monoclonal Antibody, in Healthy Subjects Challenged with Influenza A Virus in a Phase IIa Randomized Trial

2017 ◽  
Vol 57 (3) ◽  
pp. 367-377 ◽  
Author(s):  
Rong Deng ◽  
Ai Ping Lee ◽  
Mauricio Maia ◽  
Jeremy J. Lim ◽  
Tracy Burgess ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Randomized Trial ◽  
Influenza A Virus ◽  
Healthy Subjects ◽  
Influenza A

Monoclonal antibody against the universal M2 epitope of influenza A virus

2018 ◽  
Vol 102 (13) ◽  
pp. 5645-5656 ◽  
Author(s):  
Mingfang Feng ◽  
Zhuangchuan Yuan ◽  
Wenjun Xia ◽  
Xiaozhi Huang ◽  
XingBo Wang ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Influenza A Virus ◽  
Influenza A

scholarly journals A NS1-binding monoclonal antibody interacts with two residues that are highly conserved in seasonal as well as newly emerged influenza A virus

2019 ◽  
Vol 77 (1) ◽  
Author(s):  
Su Hui Catherine Teo ◽  
Jian-Ping Wu ◽  
Chee-Keng Mok ◽  
Yee-Joo Tan
Keyword(s):  
Monoclonal Antibody ◽  
Influenza A Virus ◽  
Influenza A ◽  
Rna Binding ◽  
Intracellular Localization ◽  
Cross Reactivity ◽  
Structural Protein ◽  
Multifunctional Protein ◽  
Good Target ◽  
Conformational Plasticity

Abstract The non-structural protein 1 (NS1) of influenza A virus (IAV) is a multifunctional protein that antagonizes host antiviral responses, modulating virus pathogenesis. As such, it serves as a good target for research and diagnostic assay development. In this study, we have generated a novel monoclonal antibody (mAb) 19H9 and epitope mapping revealed that two residues, P85 and Y89, of NS1 are essential for interacting with this mAb. Furthermore, residues P85 and Y89 are found to be highly conserved across different IAV subtypes, namely seasonal H1N1 and H3N2, as well as the highly pathogenic H5N1 and H5N6 avian strains. Indeed, mAb 19H9 exhibits broad cross-reactivity with IAV strains of different subtypes. The binding of mAb 19H9 to residue Y89 was further confirmed by the abrogation of interaction between NS1 and p85β. Additionally, mAb 19H9 also detected NS1 proteins expressed in IAV-infected cells, showing NS1 intracellular localization in the cytoplasm and nucleolus. To our knowledge, mAb 19H9 is the first murine mAb to bind at the juxtaposition between the N-terminal RNA-binding domain and C-terminal effector domain of NS1. It could serve as a useful research tool for studying the conformational plasticity and dynamic changes in NS1.

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