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Development and characterization of a human monoclonal antibody targeting the N-terminal region of hepatitis C virus envelope glycoprotein E1

(2018) VIROLOGY. 514. p.30-41
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Abstract
Monoclonal antibodies (mAbs) targeting the hepatitis C virus (HCV) envelope have been raised mainly against envelope protein 2 (E2), while the antigenic epitopes of envelope protein 1 (E1) are not fully identified. Here we describe the detailed characterization of a human mAb, designated A6, generated from an HCV genotype 1b infected patient. ELISA results showed reactivity of mAb A6 to full-length HCV E1E2 of genotypes 1a, 1b and 2a. Epitope mapping identified a region spanning amino acids 230-239 within the N-terminal region of E1 as critical for binding. Antibody binding to this epitope was not conformation dependent. Neutralization assays showed that mAb A6 lacks neutralizing capacity and does not interfere with the activity of known neutralizing antibodies. In summary, mAb A6 is an important tool to study the structure and function of E1 within the viral envelope, a crucial step in the development of an effective prophylactic HCV vaccine.
Keywords
Hepatitis C virus, Envelope protein, Antibody, Entry, Vaccine, CELL ENTRY, NEUTRALIZING ANTIBODIES, IN-VITRO, CONFORMATIONAL EPITOPES, LIVER-TRANSPLANTATION, E2 GLYCOPROTEINS, IMMUNE-RESPONSE, LIFE-CYCLE, INFECTION, AP33

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Chicago
Mesalam, Ahmed Atef Ahmed Abouzeid, Isabelle Desombere, Aliasghar Farhoudi Moghadam, Freya Van Houtte, Lieven Verhoye, Jonathan Ball, Jean Dubuisson, et al. 2018. “Development and Characterization of a Human Monoclonal Antibody Targeting the N-terminal Region of Hepatitis C Virus Envelope Glycoprotein E1.” Virology 514: 30–41.
APA
Mesalam, A. A. A. A., Desombere, I., Farhoudi Moghadam, A., Van Houtte, F., Verhoye, L., Ball, J., Dubuisson, J., et al. (2018). Development and characterization of a human monoclonal antibody targeting the N-terminal region of hepatitis C virus envelope glycoprotein E1. VIROLOGY, 514, 30–41.
Vancouver
1.
Mesalam AAAA, Desombere I, Farhoudi Moghadam A, Van Houtte F, Verhoye L, Ball J, et al. Development and characterization of a human monoclonal antibody targeting the N-terminal region of hepatitis C virus envelope glycoprotein E1. VIROLOGY. 2018;514:30–41.
MLA
Mesalam, Ahmed Atef Ahmed Abouzeid, Isabelle Desombere, Aliasghar Farhoudi Moghadam, et al. “Development and Characterization of a Human Monoclonal Antibody Targeting the N-terminal Region of Hepatitis C Virus Envelope Glycoprotein E1.” VIROLOGY 514 (2018): 30–41. Print.
@article{8539983,
  abstract     = {Monoclonal antibodies (mAbs) targeting the hepatitis C virus (HCV) envelope have been raised mainly against envelope protein 2 (E2), while the antigenic epitopes of envelope protein 1 (E1) are not fully identified. Here we describe the detailed characterization of a human mAb, designated A6, generated from an HCV genotype 1b infected patient. ELISA results showed reactivity of mAb A6 to full-length HCV E1E2 of genotypes 1a, 1b and 2a. Epitope mapping identified a region spanning amino acids 230-239 within the N-terminal region of E1 as critical for binding. Antibody binding to this epitope was not conformation dependent. Neutralization assays showed that mAb A6 lacks neutralizing capacity and does not interfere with the activity of known neutralizing antibodies. In summary, mAb A6 is an important tool to study the structure and function of E1 within the viral envelope, a crucial step in the development of an effective prophylactic HCV vaccine.},
  author       = {Mesalam, Ahmed Atef Ahmed Abouzeid and Desombere, Isabelle and Farhoudi Moghadam, Aliasghar and Van Houtte, Freya and Verhoye, Lieven and Ball, Jonathan and Dubuisson, Jean and Foung, Steven KH and Patel, Arvind H and Persson, Mats AA and Leroux-Roels, Geert and Meuleman, Philip},
  issn         = {0042-6822},
  journal      = {VIROLOGY},
  keyword      = {Hepatitis C virus,Envelope protein,Antibody,Entry,Vaccine,CELL ENTRY,NEUTRALIZING ANTIBODIES,IN-VITRO,CONFORMATIONAL EPITOPES,LIVER-TRANSPLANTATION,E2 GLYCOPROTEINS,IMMUNE-RESPONSE,LIFE-CYCLE,INFECTION,AP33},
  language     = {eng},
  pages        = {30--41},
  title        = {Development and characterization of a human monoclonal antibody targeting the N-terminal region of hepatitis C virus envelope glycoprotein E1},
  url          = {http://dx.doi.org/10.1016/j.virol.2017.10.019},
  volume       = {514},
  year         = {2018},
}

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