Research output: Contribution to journal › Article › Academic › peer-review
Hepatitis C virus Broadly Neutralizing Monoclonal Antibodies Isolated 25 Years after Spontaneous Clearance. / Merat, Sabrina J.; Molenkamp, Richard; Wagner, Koen et al.
In: PLoS ONE, Vol. 11, No. 10, 2016, p. e0165047.Research output: Contribution to journal › Article › Academic › peer-review
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TY - JOUR
T1 - Hepatitis C virus Broadly Neutralizing Monoclonal Antibodies Isolated 25 Years after Spontaneous Clearance
AU - Merat, Sabrina J.
AU - Molenkamp, Richard
AU - Wagner, Koen
AU - Koekkoek, Sylvie M.
AU - van de Berg, Dorien
AU - Yasuda, Etsuko
AU - Böhne, Martino
AU - Claassen, Yvonne B.
AU - Grady, Bart P.
AU - Prins, Maria
AU - Bakker, Arjen Q.
AU - de Jong, Menno D.
AU - Spits, Hergen
AU - Schinkel, Janke
AU - Beaumont, Tim
PY - 2016
Y1 - 2016
N2 - 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
AB - 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
U2 - 10.1371/journal.pone.0165047
DO - 10.1371/journal.pone.0165047
M3 - Article
C2 - 27776169
VL - 11
SP - e0165047
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 10
ER -
ID: 3005764