Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Mechanisms of Hepatitis C Virus Escape from Vaccine-Relevant Neutralizing Antibodies

Research output: Contribution to journalReviewResearchpeer-review

DOI

  1. SARS-CoV-2 Production in a Scalable High Cell Density Bioreactor

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. The role of Plasmodium falciparum variant surface antigens in protective immunity and vaccine development

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Hepatitis C virus envelope protein dynamics and the link to hypervariable region 1

    Research output: Contribution to journalReviewResearchpeer-review

  2. Antigenic and immunogenic evaluation of permutations of soluble hepatitis C virus envelope protein E2 and E1 antigens

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. In vitro adaptation and characterization of attenuated hypervariable region 1 swap chimeras of hepatitis C virus

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Global and local envelope protein dynamics of hepatitis C virus determine broad antibody sensitivity

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

Hepatitis C virus (HCV) is a major causative agent of acute and chronic hepatitis. It is estimated that 400,000 people die every year from chronic HCV infection, mostly from severe liver-related diseases such as cirrhosis and liver cancer. Although HCV was discovered more than 30 years ago, an efficient prophylactic vaccine is still missing. The HCV glycoprotein complex, E1/E2, is the principal target of neutralizing antibodies (NAbs) and, thus, is an attractive antigen for B-cell vaccine design. However, the high genetic variability of the virus necessitates the identification of conserved epitopes. Moreover, the high intrinsic mutational capacity of HCV allows the virus to continually escape broadly NAbs (bNAbs), which is likely to cause issues with vaccine-resistant variants. Several studies have assessed the barrier-to-resistance of vaccine-relevant bNAbs in vivo and in vitro. Interestingly, recent studies have suggested that escape substitutions can confer antibody resistance not only by direct modification of the epitope but indirectly through allosteric effects, which can be grouped based on the breadth of these effects on antibody susceptibility. In this review, we summarize the current understanding of HCV-specific NAbs, with a special focus on vaccine-relevant bNAbs and their targets. We highlight antibody escape studies pointing out the different methodologies and the escape mutations identified thus far. Finally, we analyze the antibody escape mechanisms of envelope protein escape substitutions and polymorphisms according to the most recent evidence in the HCV field. The accumulated knowledge in identifying bNAb epitopes as well as assessing barriers to resistance and elucidating relevant escape mechanisms may prove critical in the successful development of an HCV B-cell vaccine.

Original languageEnglish
Article number291
JournalVaccines
Volume9
Issue number3
Pages (from-to)1-19
Number of pages19
ISSN2076-393X
DOIs
Publication statusPublished - 20 Mar 2021

Bibliographical note

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

    Research areas

  • Antibody escape, B-cell vaccine, Hepatitis C virus, Virus neutralization

ID: 64730722