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

Autor: Merat SJ; AIMM Therapeutics, Amsterdam, the Netherlands., Molenkamp R; Department of Medical Microbiology, Section of Clinical Virology, Academic Medical Center, Amsterdam, the Netherlands., Wagner K; AIMM Therapeutics, Amsterdam, the Netherlands., Koekkoek SM; Department of Medical Microbiology, Section of Clinical Virology, Academic Medical Center, Amsterdam, the Netherlands., van de Berg D; AIMM Therapeutics, Amsterdam, the Netherlands., Yasuda E; AIMM Therapeutics, Amsterdam, the Netherlands., Böhne M; AIMM Therapeutics, Amsterdam, the Netherlands., Claassen YB; AIMM Therapeutics, Amsterdam, the Netherlands., Grady BP; Department of Infectious Diseases Research and Prevention, Cluster of Infectious Diseases, Public Health Service of Amsterdam, Amsterdam, the Netherlands., Prins M; 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., Bakker AQ; AIMM Therapeutics, Amsterdam, the Netherlands., de Jong MD; Department of Medical Microbiology, Section of Clinical Virology, Academic Medical Center, Amsterdam, the Netherlands., Spits H; AIMM Therapeutics, Amsterdam, the Netherlands., Schinkel J; Department of Medical Microbiology, Section of Clinical Virology, Academic Medical Center, Amsterdam, the Netherlands., Beaumont T; AIMM Therapeutics, Amsterdam, the Netherlands.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2016 Oct 24; Vol. 11 (10), pp. e0165047. Date of Electronic Publication: 2016 Oct 24 (Print Publication: 2016).
DOI: 10.1371/journal.pone.0165047
Abstrakt: 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.
Competing Interests: We would like to disclose that S.J.M, K.W., D.V.B., E.Y., M.B., Y.B.C., A.Q.B., H.S. and T.B. are employees and S.J.M, K.W., E.Y., M.B., Y.B.C., A.Q.B., H.S. and T.B. are shareholders of AIMM Therapeutics. Materials have been generated by a for profit company, AIMM Therapeutics which makes research reagents available for academic research under conditions outlined in its Material Transfer Agreement (http://www.aimmtherapeutics.com/partnering/academic-collaboration/). This does not alter our adherence to PLOS ONE policies on sharing data and materials. Furthermore, S.J.M. received travel grants from the international symposium on Hepatitis C virus and related viruses. M.D.J. was a member of the AIMM scientific advisory board.
Databáze: MEDLINE
Externí odkaz: