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J Infect Dis. 2019 Jun 4. pii: jiz274. doi: 10.1093/infdis/jiz274. [Epub ahead of print]

Repertoire and neutralizing activity of antibodies against E2 peptide in patients with spontaneous resolution of hepatitis C.

Author information

1
Laboratory for Clinical and Experimental Hepatology (LCEHep), Section of Hepatology; Clinic for Gastroenterology, University Clinic Leipzig, Leipzig, Germany.
2
German Cancer Research Center, Division of B Cell Immunology, Heidelberg, Germany.
3
Max-von-Pettenkofer-Institut, Munich, Germany.
4
Inserm U1110, University of Strasbourg, France.
5
University College London, Division of Infection and Immunity, London, UK.
6
Clinic for Hepatology and Gastroenterology, Charité, CVK, Berlin, Germany.

Abstract

Neutralizing antibodies can prevent hepatitis C virus (HCV) infection, one of the leading causes of cirrhosis and liver cancer. Here, we characterized the immunoglobulin repertoire of memory B cell antibodies against a linear epitope in the central front layer of HCV envelope (E2) (aa483-499) in patients that were infected in a single-source outbreak. A reverse transcriptase (RT)-PCR based immunoglobulin gene cloning and recombinant expression approach was applied to express monoclonal antibodies from HCV E2-peptide-binding IgG+ memory B cells. We identified highly mutated antibodies with neutralizing effect in vitro against different genotype isolates sharing similar gene features. Our data confirm the importance of VH1-69 usage for neutralizing activity. The data offers a promising basis for vaccine research and the use of anti-E2 antibodies as a mean of passive immunization.

KEYWORDS:

HCV; HCV envelope (E2) protein; anti-D cohort; memory B cells; neutralizing antibodies

PMID:
31165162
DOI:
10.1093/infdis/jiz274

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