Project A07 (Associated)

Principal Investigator

Prof. Dr. Thomas Krey

Universität zu Lübeck

A7

PhD candidate

Frithjof Besa


A7

Project Summary

Structural Characterization of HCV-Antibody Interactions

Hepatitis C virus (HCV) has infected an estimated 58 million people worldwide and is therefore a global health burden [1]. While drugs to treat an HCV infection are available, a vaccine to control the spread of the virus is still missing [2]. Besides additional immune evasion mechanisms, the genetic diversity of HCV represents a major challenge in vaccine design [3,4]. It is known that the HCV glycoprotein E2 induces neutralizing antibody responses, which differ in strength depending on the E2 sequence. This project aims to gain insights into the determinants of immunogenicity inherent to the HCV E1/E2 heterodimer. To reach this goal, the heterodimer will be produced in complex with potent neutralizing antibodies identified from chronically infected HCV patients and the resulting complex structurally characterized by cryo-electron microscopy. The expected results will pave the way for informed vaccine design.

References

1. World Health Organisation. Global hepatitis report 2024
2. Vermehren J, Park JS, Jacobson IM, et al. Challenges and perspectives of direct antivirals for the treatment of hepatitis C virus infection. J Hepatol. 2018 Nov;69(5):1178-1187. doi: 10.1016/j.jhep.2018.07.002.  
3. Bankwitz D, Bahai A, Labuhn M, et al. Hepatitis C reference viruses highlight potent antibody responses and diverse viral functional interactions with neutralising antibodies. Gut. 2021 Sep;70(9):1734-1745. doi: 10.1136/gutjnl-2020-321190. Epub 2020 Dec 15. Erratum in: Gut. 2024 Jan 5;73(2):e1. doi: 10.1136/gutjnl-2020-321190corr1.
4. Fuerst TR, Pierce BG, Keck ZY, et al. Designing a B Cell-Based Vaccine against a Highly Variable Hepatitis C Virus. Front Microbiol. 2018 Jan 15;8:2692. doi: 10.3389/fmicb.2017.02692.