[HTML][HTML] Hepatitis C virus Broadly Neutralizing Monoclonal Antibodies Isolated 25 Years after Spontaneous Clearance

SJ Merat, R Molenkamp, K Wagner, SM Koekkoek… - PLoS …, 2016 - journals.plos.org
SJ Merat, R Molenkamp, K Wagner, SM Koekkoek, D van de Berg, E Yasuda, M Böhne…
PLoS One, 2016journals.plos.org
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 …
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.
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