scholarly journals Broad betacoronavirus neutralization by a stem helix–specific human antibody

Science ◽  
2021 ◽  
pp. eabj3321
Author(s):  
Dora Pinto ◽  
Maximilian M. Sauer ◽  
Nadine Czudnochowski ◽  
Jun Siong Low ◽  
M. Alejandra Tortorici ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Membrane Fusion ◽  
Molecular Basis ◽  
Somatic Mutations ◽  
Cross Reactivity ◽  
Human Antibody ◽  
Viral Neutralization ◽  
Effector Functions ◽  
Functional Studies ◽  
Viral Burden

The spillovers of β-coronaviruses in humans and the emergence of SARS-CoV-2 variants highlight the need for broad coronavirus countermeasures. We describe five monoclonal antibodies (mAbs) cross-reacting with the stem helix of multiple β-coronavirus spike glycoproteins isolated from COVID-19 convalescent individuals. Using structural and functional studies we show that the mAb with the greatest breadth (S2P6) neutralizes pseudotyped viruses from three different subgenera through inhibition of membrane fusion and delineate the molecular basis for its cross-reactivity. S2P6 reduces viral burden in hamsters challenged with SARS-CoV-2 through viral neutralization and Fc-mediated effector functions. Stem helix antibodies are rare, oftentimes of narrow specificity and can acquire neutralization breadth through somatic mutations. These data provide a framework for structure-guided design of pan-β-coronavirus vaccines eliciting broad protection.

scholarly journals A human antibody that broadly neutralizes betacoronaviruses protects against SARS-CoV-2 by blocking the fusion machinery

2021 ◽  
Author(s):  
Dora Pinto ◽  
Maximilian M. Sauer ◽  
Nadine Czudnochowski ◽  
Jun Siong Low ◽  
M. Alejandra Tortorici ◽  
...  
Keyword(s):  
Viral Entry ◽  
Cross Reactivity ◽  
Human Antibody ◽  
Cell Repertoire ◽  
Viral Neutralization ◽  
Effector Functions ◽  
Functional Studies ◽  
B Cell Repertoire ◽  
Protective Antibodies ◽  
Rapid Emergence

The repeated spillovers of β-coronaviruses in humans along with the rapid emergence of SARS-CoV-2 escape variants highlight the need to develop broad coronavirus therapeutics and vaccines. Five monoclonal antibodies (mAbs) were isolated from COVID-19 convalescent individuals and found to cross-react with multiple β-coronavirus spike (S) glycoproteins by targeting the stem helix. One of these mAbs, S2P6, cross-reacts with more than twenty human and animal β-coronavirus S glycoproteins and broadly neutralizes SARS-CoV-2 and pseudotyped viruses from the sarbecovirus, merbecovirus and embecovirus subgenera. Structural and functional studies delineate the molecular basis of S2P6 cross-reactivity and broad neutralization and indicate that this mAb blocks viral entry through inhibition of membrane fusion. S2P6 protects hamsters challenged with SARS-CoV-2 (including the B.1.351 variant of concern) through viral neutralization and Fc-mediated effector functions. Serological and B cell repertoire analyses indicate that antibodies targeting the stem helix are found in some convalescent donors and vaccinees but are predominantly of narrow specificity. Germline reversion of the identified cross-reactive mAbs revealed that their unmutated ancestors are specific for the endemic OC43 or HKU1 viruses and acquired enhanced affinity and breadth through somatic mutations. These data demonstrate that conserved epitopes in the coronavirus fusion machinery can be targeted by protective antibodies and provide a framework for structure-guided design of pan-β-coronavirus vaccines eliciting broad protection.

scholarly journals Identification and Characterization of Broadly Neutralizing Human Monoclonal Antibodies Directed against the E2 Envelope Glycoprotein of Hepatitis C Virus

2009 ◽  
Vol 83 (23) ◽  
pp. 12473-12482 ◽  
Author(s):  
Teresa J. Broering ◽  
Kerry A. Garrity ◽  
Naomi K. Boatright ◽  
Susan E. Sloan ◽  
Frantisek Sandor ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Envelope Glycoprotein ◽  
Cross Reactivity ◽  
Human Antibody ◽  
Human Monoclonal Antibodies ◽  
Genotype 1A ◽  
Neutralizing Monoclonal Antibody

ABSTRACT Nearly all livers transplanted into hepatitis C virus (HCV)-positive patients become infected with HCV, and 10 to 25% of reinfected livers develop cirrhosis within 5 years. Neutralizing monoclonal antibody could be an effective therapy for the prevention of infection in a transplant setting. To pursue this treatment modality, we developed human monoclonal antibodies (HuMAbs) directed against the HCV E2 envelope glycoprotein and assessed the capacity of these HuMAbs to neutralize a broad panel of HCV genotypes. HuMAb antibodies were generated by immunizing transgenic mice containing human antibody genes (HuMAb mice; Medarex Inc.) with soluble E2 envelope glycoprotein derived from a genotype 1a virus (H77). Two HuMAbs, HCV1 and 95-2, were selected for further study based on initial cross-reactivity with soluble E2 glycoproteins derived from genotypes 1a and 1b, as well as neutralization of lentivirus pseudotyped with HCV 1a and 1b envelope glycoproteins. Additionally, HuMAbs HCV1 and 95-2 potently neutralized pseudoviruses from all genotypes tested (1a, 1b, 2b, 3a, and 4a). Epitope mapping with mammalian and bacterially expressed proteins, as well as synthetic peptides, revealed that HuMAbs HCV1 and 95-2 recognize a highly conserved linear epitope spanning amino acids 412 to 423 of the E2 glycoprotein. The capacity to recognize and neutralize a broad range of genotypes, the highly conserved E2 epitope, and the fully human nature of the antibodies make HuMAbs HCV1 and 95-2 excellent candidates for treatment of HCV-positive individuals undergoing liver transplantation.

scholarly journals Development of a Colloidal Gold Immunochromatographic Assay for Duck Enteritis Virus Detection Using Monoclonal Antibodies

Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 365
Author(s):  
Fengli Liu ◽  
Yanxin Cao ◽  
Maokai Yan ◽  
Mengxu Sun ◽  
Qingshui Zhang ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Colloidal Gold ◽  
Preventive Intervention ◽  
Virus Detection ◽  
Cross Reactivity ◽  
Duck Enteritis Virus ◽  
Detection Sensitivity ◽  
Immunochromatographic Assay ◽  
Efficient Detection ◽  
Enteritis Virus

Duck viral enteritis is a highly contagious and fatal disease of commercial waterfowl flocks. The disease occurs sporadically or epizootically in mainland China due to insufficient vaccinations. Early and rapid diagnosis is important for preventive intervention and the control of epizootic events in clinical settings. In this study, we generated two monoclonal antibodies (MAbs) that specifically recognized the duck enteritis virus (DEV) envelope glycoprotein B and tegument protein UL47, respectively. Using these MAbs, a colloidal gold-based immunochromatographic assay (ICA) was developed for the efficient detection of DEV antigens within 15 min. Our results showed that the detection limit of the developed ICA strip was 2.52 × 103 TCID50/mL for the virus infected cell culture suspension with no cross-reactivity with other pathogenic viruses commonly encountered in commercially raised waterfowl. Using samples from experimentally infected ducks, we demonstrated that the ICA detected the virus in cloacal swab samples on day three post-infection, demonstrating an 80% concordance with the PCR. For tissue homogenates from ducks succumbing to infection, the detection sensitivity was 100%. The efficient and specific detection by this ICA test provides a valuable, convenient, easy to use and rapid diagnostic tool for DVE under both laboratory and field conditions.

scholarly journals Monoclonal antibodies to bovine UDP-galactosyltransferase. Characterization, cross-reactivity, and utilization as structural probes.

1986 ◽  
Vol 261 (17) ◽  
pp. 7975-7981
Author(s):  
J T Ulrich ◽  
J R Schenck ◽  
H G Rittenhouse ◽  
N L Shaper ◽  
J H Shaper
Keyword(s):  
Monoclonal Antibodies ◽  
Cross Reactivity ◽  
Structural Probes

scholarly journals Screening and development of monoclonal antibodies for identification of ferret T follicular helper cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wenbo Jiang ◽  
Julius Wong ◽  
Hyon-Xhi Tan ◽  
Hannah G. Kelly ◽  
Paul G. Whitney ◽  
...  
Keyword(s):  
Animal Model ◽  
Monoclonal Antibodies ◽  
Lymph Node ◽  
Cross Reactivity ◽  
Tfh Cells ◽  
Follicular Helper ◽  
Lymph Node Cells ◽  
Human Viruses ◽  
Humoral Responses ◽  
Murine Monoclonal Antibodies

AbstractThe ferret is a key animal model for investigating the pathogenicity and transmissibility of important human viruses, and for the pre‐clinical assessment of vaccines. However, relatively little is known about the ferret immune system, due in part to a paucity of ferret‐reactive reagents. In particular, T follicular helper (Tfh) cells are critical in the generation of effective humoral responses in humans, mice and other animal models but to date it has not been possible to identify Tfh in ferrets. Here, we describe the screening and development of ferret-reactive BCL6, CXCR5 and PD-1 monoclonal antibodies. We found two commercial anti-BCL6 antibodies (clone K112-91 and clone IG191E/A8) had cross-reactivity with lymph node cells from influenza-infected ferrets. We next developed two murine monoclonal antibodies against ferret CXCR5 (clone feX5-C05) and PD-1 (clone fePD-CL1) using a single B cell PCR-based method. We were able to clearly identify Tfh cells in lymph nodes from influenza infected ferrets using these antibodies. The development of ferret Tfh marker antibodies and the identification of ferret Tfh cells will assist the evaluation of vaccine-induced Tfh responses in the ferret model and the design of novel vaccines against the infection of influenza and other viruses, including SARS-CoV2.

scholarly journals Cross-Reactivity and Neutralizing Ability of Monoclonal Antibodies against Microcystins

1994 ◽  
Vol 38 (5) ◽  
pp. 389-392 ◽  
Author(s):  
Shinji Saito ◽  
Yasunobu Nakano ◽  
Katsutoshi Kushida ◽  
Makoto Shirai ◽  
Ken-ichi Harada ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Cross Reactivity

Interspecies cross-reactivity of monoclonal antibodies to various epitopes of human plasminogen

1984 ◽  
Vol 230 (1) ◽  
pp. 306-315 ◽  
Author(s):  
Helen S. Cummings ◽  
Victoria A. Ploplis ◽  
John M. Beals ◽  
Francis J. Castellino
Keyword(s):  
Monoclonal Antibodies ◽  
Cross Reactivity ◽  
Human Plasminogen

scholarly journals Characterization of components of Z-bands in the fibrillar flight muscle of Drosophila melanogaster.

1989 ◽  
Vol 109 (5) ◽  
pp. 2157-2167 ◽  
Author(s):  
J D Saide ◽  
S Chin-Bow ◽  
J Hogan-Sheldon ◽  
L Busquets-Turner ◽  
J O Vigoreaux ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Monoclonal Antibodies ◽  
Flight Muscle ◽  
Cross Reactivity ◽  
Antigenic Determinants ◽  
Immunogold Staining ◽  
Thick Filaments ◽  
The Matrix ◽  
Flight Muscles

Twelve monoclonal antibodies have been raised against proteins in preparations of Z-disks isolated from Drosophila melanogaster flight muscle. The monoclonal antibodies that recognized Z-band components were identified by immunofluorescence microscopy of flight muscle myofibrils. These antibodies have identified three Z-disk antigens on immunoblots of myofibrillar proteins. Monoclonal antibodies alpha:1-4 recognize a 90-100-kD protein which we identify as alpha-actinin on the basis of cross-reactivity with antibodies raised against honeybee and vertebrate alpha-actinins. Monoclonal antibodies P:1-4 bind to the high molecular mass protein, projectin, a component of connecting filaments that link the ends of thick filaments to the Z-band in insect asynchronous flight muscles. The anti-projectin antibodies also stain synchronous muscle, but, surprisingly, the epitopes here are within the A-bands, not between the A- and Z-bands, as in flight muscle. Monoclonal antibodies Z(210):1-4 recognize a 210-kD protein that has not been previously shown to be a Z-band structural component. A fourth antigen, resolved as a doublet (approximately 400/600 kD) on immunoblots of Drosophila fibrillar proteins, is detected by a cross reacting antibody, Z(400):2, raised against a protein in isolated honeybee Z-disks. On Lowicryl sections of asynchronous flight muscle, indirect immunogold staining has localized alpha-actinin and the 210-kD protein throughout the matrix of the Z-band, projectin between the Z- and A-bands, and the 400/600-kD components at the I-band/Z-band junction. Drosophila alpha-actinin, projectin, and the 400/600-kD components share some antigenic determinants with corresponding honeybee proteins, but no honeybee protein interacts with any of the Z(210) antibodies.

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