Next-Generation Vaccine Design

The project focuses on developing next-generation vaccines. For several viruses, traditional vaccine platforms fail to elicit a strong protective immune response, for example, due to the conformational flexibility of the immunogen or the low immunogenicity of recombinant proteins. This project aims to identify, develop and engineer enhanced, stabilised protein-based immunogens that, ideally, expose broadly conserved neutralising epitopes. Where necessary, immunogen design will involve displaying them on the surface of multivalent nanoparticle carriers (such as ferritin, synthetic polymers or AI-driven self-assembling nanoparticles) to effectively activate B cells. In light of the recent SARS-CoV-2 pandemic and the persistence of respiratory pathogens, there is an urgent need for vaccines that provide better, ideally ‘sterilising immunity’, preventing infection entirely rather than merely reducing the severity of the disease. Next-generation vaccines offer a way to halt transmission and provide broader protection, thereby reducing the global burden of infectious diseases and decreasing reliance on repeated systemic booster doses.

Specific questions relating to the project to be answered by the candidate for evaluation purposes:

• How can we select a suitable immunogen and optimise it?

• Which experimental assays might be appropriate for stabilisation and validation?

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

During the six-month placement, the candidate will undertake:

• Literature review: In-depth study of current vaccine platforms and their immunological impact

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

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

• Writing: Documenting protocols and drafting the final report.

The candidate will be an active member of the Krey Lab, attending weekly research group meetings to present their progress and receive feedback. The candidate is expected to take part 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.

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