scholarly journals Characterization of Human Monoclonal Antibodies Specific to the Hepatitis C Virus Glycoprotein E2 within VitroBinding Neutralization Properties

Virology ◽  
1998 ◽  
Vol 249 (1) ◽  
pp. 32-41 ◽  
Author(s):  
François Habersetzer ◽  
Anne Fournillier ◽  
Jean Dubuisson ◽  
Domenico Rosa ◽  
Sergio Abrignani ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Human Monoclonal Antibodies ◽  
Virus Glycoprotein ◽  
Glycoprotein E2

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.

Isolation and Epitope Characterization of Human Monoclonal Antibodies to Hepatitis C Virus Core Antigen

Hybridoma ◽  
1994 ◽  
Vol 13 (1) ◽  
pp. 9-13 ◽  
Author(s):  
KARL SIEMONEIT ◽  
MARCIA DA SILVA CARDOSO ◽  
ALOIS WÖLPL ◽  
KLAUS KOERNER ◽  
BERNHARD KUBANEK
Keyword(s):  
Monoclonal Antibodies ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Core Antigen ◽  
Human Monoclonal Antibodies ◽  
Virus Core ◽  
Epitope Characterization

scholarly journals Expression and Characterization of a Minimal Hepatitis C Virus Glycoprotein E2 Core Domain That Retains CD81 Binding

2007 ◽  
Vol 81 (17) ◽  
pp. 9584-9590 ◽  
Author(s):  
Kathleen McCaffrey ◽  
Irene Boo ◽  
Pantelis Poumbourios ◽  
Heidi E. Drummer
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Variable Region ◽  
Sequence Comparisons ◽  
Variable Regions ◽  
Core Domain ◽  
Virus Glycoprotein ◽  
Glycoprotein E2 ◽  
Cd81 Binding

ABSTRACT The hepatitis C virus glycoprotein E2 receptor-binding domain is encompassed by amino acids 384 to 661 (E2661) and contains two hypervariable sequences, HVR1 and HVR2. E2 sequence comparisons revealed a third variable region, located between residues 570 and 580, that varies widely between genotypes, designated here as igVR, the intergenotypic variable region. A secreted E2661 glycoprotein with simultaneous deletions of the three variable sequences retained its ability to bind CD81 and conformation-dependent monoclonal antibodies (MAbs) and displayed enhanced binding to a neutralizing MAb directed to E2 immunogenic domain B. Our data provide insights into the E2 structure by suggesting that the three variable regions reside outside a conserved E2 core.

scholarly journals Isolation and Characterization of Broadly Neutralizing Human Monoclonal Antibodies to the E1 Glycoprotein of Hepatitis C Virus

2007 ◽  
Vol 82 (2) ◽  
pp. 966-973 ◽  
Author(s):  
Jean-Christophe Meunier ◽  
Rodney S. Russell ◽  
Vera Goossens ◽  
Sofie Priem ◽  
Hugo Walter ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Neutralizing Antibodies ◽  
Hcv Infection ◽  
Envelope Glycoproteins ◽  
Human Monoclonal Antibodies ◽  
Humoral And Cellular Immunity ◽  
Isolation And Characterization

ABSTRACT The relative importance of humoral and cellular immunity in the prevention or clearance of hepatitis C virus (HCV) infection is poorly understood. However, there is considerable evidence that neutralizing antibodies are involved in disease control. Here we describe the detailed analysis of human monoclonal antibodies (MAbs) directed against HCV glycoprotein E1, which may have the potential to control HCV infection. We have identified two MAbs that can strongly neutralize HCV-pseudotyped particles (HCVpp) bearing the envelope glycoproteins of genotypes 1a, 1b, 4a, 5a, and 6a and less strongly neutralize HCVpp bearing the envelope glycoproteins of genotype 2a. Genotype 3a was not neutralized. The epitopes for both MAbs were mapped to the region encompassing amino acids 313 to 327. In addition, robust neutralization was also observed against cell culture-adapted viruses of genotypes 1a and 2a. Results from this study suggest that these MAbs may have the potential to prevent HCV infection.

scholarly journals Characterization of Functional Hepatitis C Virus Envelope Glycoproteins

2004 ◽  
Vol 78 (6) ◽  
pp. 2994-3002 ◽  
Author(s):  
Anne Op De Beeck ◽  
Cécile Voisset ◽  
Birke Bartosch ◽  
Yann Ciczora ◽  
Laurence Cocquerel ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Conformational Changes ◽  
Structural Changes ◽  
Envelope Proteins ◽  
Viral Envelope ◽  
Envelope Glycoproteins ◽  
Functional Envelope

ABSTRACT Hepatitis C virus (HCV) encodes two envelope glycoproteins, E1 and E2, that assemble as a noncovalent heterodimer which is mainly retained in the endoplasmic reticulum. Because assembly into particles and secretion from the cell lead to structural changes in viral envelope proteins, characterization of the proteins associated with the virion is necessary in order to better understand how they mature to be functional in virus entry. There is currently no efficient and reliable cell culture system to amplify HCV, and the envelope glycoproteins associated with the virion have therefore not been characterized yet. Recently, infectious pseudotype particles that are assembled by displaying unmodified HCV envelope glycoproteins on retroviral core particles have been successfully generated. Because HCV pseudotype particles contain fully functional envelope glycoproteins, these envelope proteins, or at least a fraction of them, should be in a mature conformation similar to that on the native HCV particles. In this study, we used conformation-dependent monoclonal antibodies to characterize the envelope glycoproteins associated with HCV pseudotype particles. We showed that the functional unit is a noncovalent E1E2 heterodimer containing complex or hybrid type glycans. We did not observe any evidence of maturation by a cellular endoprotease during the transport of these envelope glycoproteins through the secretory pathway. These envelope glycoproteins were recognized by a panel of conformation-dependent monoclonal antibodies as well as by CD81, a molecule involved in HCV entry. The functional envelope glycoproteins associated with HCV pseudotype particles were also shown to be sensitive to low-pH treatment. Such conformational changes are likely necessary to initiate fusion.

scholarly journals Hepatitis C Virus Glycoprotein E2 Binding to CD81: The Role of E1E2 Cleavage and Protein Glycosylation in Bioactivity

Virology ◽  
2000 ◽  
Vol 273 (1) ◽  
pp. 60-66 ◽  
Author(s):  
Christine Chan-Fook ◽  
Wen-Rong Jiang ◽  
Berwyn E. Clarke ◽  
Nicole Zitzmann ◽  
Catherine Maidens ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Protein Glycosylation ◽  
Virus Glycoprotein ◽  
Glycoprotein E2
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