Next-Generation Vaccine Design

Prof. Thomas Krey – Department of Biochemistry

The Krey Lab operates at the intersection of Biochemistry, Structural Biology, and Immunology. One of the group's primary research interests is the design and optimization of efficient next-generation vaccines against major human pathogens, including hepatitis C virus (HCV), hepatitis E virus (HEV), human cytomegalovirus (HCMV), and other pathogenic viruses.

This research is part of the human medicine-centered Life Sciences (STEM) of the University of Lübeck in the area of infection biology. The lab bridges fundamental biochemical research (protein folding, structure and stability, protein-protein interactions, and the biochemistry of immune responses) with translational medicine (vaccine development), thereby contributing to the University of Lübeck’s goal of advancing personalized, highly effective therapeutic interventions.

Project Overview

The project focuses on developing next-generation vaccines. For several viruses, traditional vaccine platforms fail to elicit a strong protective immune response, e.g., due to the immunogen’s conformational flexibility or the low immunogenicity of recombinant proteins. This project aims to identify, develop and engineer enhanced, stabilized protein-based immunogens that ideally expose broadly conserved neutralization epitopes. If required, immunogen design will involve the display on the surface of multivalent nanoparticle carriers (such as ferritin, synthetic polymers, or AI-driven self-assembling nanoparticles) to effectively activate B cells. With the recent SARS-CoV-2 pandemic and the persistence of respiratory pathogens, there is an urgent need for vaccines that provide better, ideally "sterilizing immunity," preventing infection entirely rather than just reducing severe disease. Next-generation vaccines offer a path to stop transmission and provide broader protection, reducing the global burden of infectious diseases and decreasing reliance on repeated systemic boosters.

Concrete questions related to the project to be answered by the candidate for evaluation purposes:

  • How can we choose a suitable immunogen and optimize it? 

  • Which experimental assays could be appropriate for stabilization and validation?

  • To what extent do you expect the stability of the engineered protein complex to correlate with its immunogenicity?

Description of Activities

During the six-month stay, the candidate will engage in:

  • Literature Review: Intensive study of current vaccine platforms and their immunologic impact

  • Experiments:  Construct design, cloning, cell culture, protein expression and purification by chromatography, and protein characterization using biochemical, biophysical, and structural methods (e.g., ELISA, SEC-MALLS, DLS, X-ray crystallography, cryo-EM)

  • Computational Modeling: Basic structural analysis of protein-protein interactions using software such as PyMOL and AlphaFold3.

  • Writing: Documenting protocols and writing the final report.

Integration and Independence

The candidate will be an active member of the Krey Lab, attending weekly research group meetings to present progress and receive feedback. The candidate is expected to participate in departmental seminars and collaborate with lab members on shared laboratory tasks. At the same time, the candidate is expected to take ownership of the specific project and of drafting the theoretical proposal.

Relevant Infrastructure and Resources

The candidate will have access to the Biochemistry Department’s state-of-the-art facilities.

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