Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

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

Publikation: Bidrag til tidsskriftReviewForskningpeer review

DOI

  1. COVID-19 Vaccination Might Induce Reversible Cerebral Vasoconstriction Syndrome Attacks: A Case Report

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. High-Titer Hepatitis C Virus Production in a Scalable Single-Use High Cell Density Bioreactor

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Small molecule inhibitors of mertk and flt3 induce cell cycle arrest in human cd8+ t cells

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Impact of COVID-19 Disruptions on Global BCG Coverage and Paediatric TB Mortality: A Modelling Study

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Inactivated whole hepatitis C virus vaccine employing a licensed adjuvant elicits cross-genotype neutralizing antibodies in mice

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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

    Publikation: Bidrag til tidsskriftReviewForskningpeer review

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

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

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.

OriginalsprogEngelsk
Artikelnummer291
TidsskriftVaccines
Vol/bind9
Udgave nummer3
Sider (fra-til)1-19
Antal sider19
ISSN2076-393X
DOI
StatusUdgivet - 20 mar. 2021

Bibliografisk note

Funding Information:
This manuscript was supported by a postdoc grant from the Lundbeck Foundation (R303-2018-3396 To RVM), a Ph.D. stipend from the Candy Foundation (CHO), an Experiment grant from the Lundbeck Foundation (grant number: R324-2019-1375 to JP) and a Lundbeck Foundation Fellowship (grant number: R335-2019-2052 to JP).

ID: 64730722