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Non-random Escape Pathways from a Broadly Neutralizing Human Monoclonal Antibody Map to a Highly Conserved Region on the Hepatitis C Virus E2 Glycoprotein Encompassing Amino Acids 412–423


An effective hepatitis C virus (HCV) vaccine will require information on epitopes that are responsible for protective antibodies against this highly diverse virus. A region known to be highly conserved and responsible for broadly neutralizing antibodies is located on the E2 glycoprotein at 412–423. To test whether HCV can escape from human antibodies against this region, infectious virus was passaged in culture in increasing concentrations of a human monoclonal antibody to 412–423. Multiple pathways of viral escape were identified at different levels of antibody concentrations. Some of the escape virions were stable and were more robust than wild-type virus. Other escape virions were unstable and had compromised in vitro viral fitness. Collectively, these findings underscore the difficulties in HCV vaccine development and the need to induce high potency antibodies not associated with viral escape.


Vyšlo v časopise: Non-random Escape Pathways from a Broadly Neutralizing Human Monoclonal Antibody Map to a Highly Conserved Region on the Hepatitis C Virus E2 Glycoprotein Encompassing Amino Acids 412–423. PLoS Pathog 10(8): e32767. doi:10.1371/journal.ppat.1004297
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004297

Souhrn

An effective hepatitis C virus (HCV) vaccine will require information on epitopes that are responsible for protective antibodies against this highly diverse virus. A region known to be highly conserved and responsible for broadly neutralizing antibodies is located on the E2 glycoprotein at 412–423. To test whether HCV can escape from human antibodies against this region, infectious virus was passaged in culture in increasing concentrations of a human monoclonal antibody to 412–423. Multiple pathways of viral escape were identified at different levels of antibody concentrations. Some of the escape virions were stable and were more robust than wild-type virus. Other escape virions were unstable and had compromised in vitro viral fitness. Collectively, these findings underscore the difficulties in HCV vaccine development and the need to induce high potency antibodies not associated with viral escape.


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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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