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

被引:35
作者
Merat, Sabrina J. [1 ]
Molenkamp, Richard [2 ]
Wagner, Koen [1 ]
Koekkoek, Sylvie M. [2 ]
de Berg, Dorien van [1 ]
Yasuda, Etsuko [1 ]
Bohne, Martino [1 ]
Claassen, Yvonne B. [1 ]
Grady, Bart P. [3 ]
Prins, Maria [3 ,4 ]
Bakker, Arjen Q. [1 ]
de Jong, Menno D. [2 ]
Spits, Hergen [1 ]
Schinkel, Janke [2 ]
Beaumont, Tim [1 ]
机构
[1] AIMM Therapeut, Amsterdam, Netherlands
[2] Acad Med Ctr, Dept Med Microbiol, Sect Clin Virol, Amsterdam, Netherlands
[3] Publ Hlth Serv Amsterdam, Dept Infect Dis Res & Prevent, Cluster Infect Dis, Amsterdam, Netherlands
[4] Acad Med Ctr, Dept Infect Dis, Amsterdam, Netherlands
来源
PLOS ONE | 2016年 / 11卷 / 10期
关键词
SINGLE-SOURCE OUTBREAK; CHRONIC HCV; IMMUNE-RESPONSES; VIRAL CLEARANCE; DRUG-USERS; GLYCOPROTEIN; INFECTION; SOFOSBUVIR; EPITOPE; RIBAVIRIN;
D O I
10.1371/journal.pone.0165047
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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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