We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Hepatitis C virus Broadly Neutralizing Monoclonal Antibodies Isolated 25 Years after Spontaneous Clearance.
- Authors
Merat, Sabrina J.; Molenkamp, Richard; Wagner, Koen; Koekkoek, Sylvie M.; van de Berg, Dorien; Yasuda, Etsuko; Böhne, Martino; Claassen, Yvonne B.; Grady, Bart P.; Prins, Maria; Bakker, Arjen Q.; de Jong, Menno D.; Spits, Hergen; Schinkel, Janke; Beaumont, Tim
- 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.
- Subjects
HEPATITIS C virus; MONOCLONAL antibodies; B cells; INTRAVENOUS drug abusers; HEPATITIS C vaccines
- Publication
PLoS ONE, 2016, Vol 11, Issue 10, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0165047