Determinants of protective immunity in HCV: A gold standard for vaccine development

About this project

In a small number of HCV patients, strong immune responses lead to control and eventual elimination of the viral infection. However, the properties of this natural immune protection are not well understood. Most importantly, the role of antibodies in HCV protection is not clearly defined. Therefore, supported by the DZIF HCV vaccine project, we investigate how antibodies protect against HCV infection. What are the properties of the antibodies that are generated during HCV infection that heal? How do these antibodies differ from those produced when the infection becomes chronic? Are different areas of viral envelope proteins attacked? What factors influence the formation of particularly good antibodies, and how good are the antibodies that induce vaccine candidates? We are investigating these questions to develop a vaccine that induces particularly good protective antibodies.
To develop a precise measure of protective immunity, we first isolated antibodies from the blood of 104 HCV-positive patients and then screened them for their neutralizing properties against as many different HCV variants as possible. Using bioinformatics, we learned that variants respond differently to antibodies, regardless of their genetic background. Our results may help develop a broadly effective vaccine in the future and assess the efficacy of vaccine candidates.

In collaboration with the Florian Klein Laboratory (Cologne), we recently used this system to isolate highly potent and broadly neutralizing antibodies from HCV patients (Weber et al. Immunity 2022).  With funding from the DFG, DZIF, and the Helmholtz Association, we expand on this knowledge to develop HCV vaccine candidates.