title: Hepatitis C virus Broadly Neutralizing Monoclonal Antibodies Isolated 25 Years after Spontaneous Clearance.
abstract: Hepatitis C virus (HCV) is world-wide a major cause of liver related morbidity and mortality. No vaccine is available to prevent HCV infection. To design an effective vaccine, understanding immunity against HCV is necessary. The memory B cell repertoire was characterized from an intravenous drug user who spontaneously cleared HCV infection 25 years ago. CD27+IgG+ memory B cells were immortalized using BCL6 and Bcl-xL. These immortalized B cells were used to study antibody-mediated immunity against the HCV E1E2 glycoproteins. Five E1E2 broadly reactive antibodies were isolated: 3 antibodies showed potent neutralization of genotype 1 to 4 using HCV pseudotyped particles, whereas the other 2 antibodies neutralized genotype 1, 2 and 3 or 1 and 2 only. All antibodies recognized non-linear epitopes on E2. Finally, except for antibody AT12-011, which recognized an epitope consisting of antigenic domain C /AR2 and AR5, all other four antibodies recognized epitope II and domain B. These data show that a subject, who spontaneously cleared HCV infection 25 years ago, still has circulating memory B cells that are able to secrete broadly neutralizing antibodies. Presence of such memory B cells strengthens the argument for undertaking the development of an HCV vaccine.
authors: AIMM Therapeutics, Amsterdam, the Netherlands.
authors: Sabrina J
authors: SJ
authors: Merat
authors: Department of Medical Microbiology, Section of Clinical Virology, Academic Medical Center, Amsterdam, the Netherlands.
authors: Richard
authors: R
authors: Molenkamp
authors: AIMM Therapeutics, Amsterdam, the Netherlands.
authors: Koen
authors: K
authors: Wagner
authors: Department of Medical Microbiology, Section of Clinical Virology, Academic Medical Center, Amsterdam, the Netherlands.
authors: Sylvie M
authors: SM
authors: Koekkoek
authors: AIMM Therapeutics, Amsterdam, the Netherlands.
authors: Dorien
authors: D
authors: van de Berg
authors: AIMM Therapeutics, Amsterdam, the Netherlands.
authors: Etsuko
authors: E
authors: Yasuda
authors: AIMM Therapeutics, Amsterdam, the Netherlands.
authors: Martino
authors: M
authors: Böhne
authors: AIMM Therapeutics, Amsterdam, the Netherlands.
authors: Yvonne B
authors: YB
authors: Claassen
authors: Department of Infectious Diseases Research and Prevention, Cluster of Infectious Diseases, Public Health Service of Amsterdam, Amsterdam, the Netherlands.
authors: Bart P
authors: BP
authors: Grady
authors: Department of Infectious Diseases Research and Prevention, Cluster of Infectious Diseases, Public Health Service of Amsterdam, Amsterdam, the Netherlands.|Department of infectious diseases, Academic Medical Center, Amsterdam, the Netherlands.
authors: Maria
authors: M
authors: Prins
authors: AIMM Therapeutics, Amsterdam, the Netherlands.
authors: Arjen Q
authors: AQ
authors: Bakker
authors: Department of Medical Microbiology, Section of Clinical Virology, Academic Medical Center, Amsterdam, the Netherlands.
authors: Menno D
authors: MD
authors: de Jong
authors: AIMM Therapeutics, Amsterdam, the Netherlands.
authors: Hergen
authors: H
authors: Spits
authors: Department of Medical Microbiology, Section of Clinical Virology, Academic Medical Center, Amsterdam, the Netherlands.
authors: Janke
authors: J
authors: Schinkel
authors: AIMM Therapeutics, Amsterdam, the Netherlands.
authors: Tim
authors: T
authors: Beaumont
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000302:isolation & purification*; D057134:Antibodies, Neutralizing / Q000302:isolation & purification*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006526:Hepatitis C / Q000097:blood* / Q000628:therapy; D018937:Hepatitis C Antibodies / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D015819:Substance Abuse, Intravenous / Q000821:virology; D014759:Viral Envelope Proteins / Q000276:immunology*; D014761:Viral Hepatitis Vaccines / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000939:Epitopes; D018937:Hepatitis C Antibodies; D014759:Viral Envelope Proteins; D014761:Viral Hepatitis Vaccines