The set of structural and biophysical tools we use are broadly applicable to a wide range of systems and are particularly powerful in providing structural information for proteins under native solution conditions. This versatility gives us a significant new window into vaccine immunogen structure that can be used for antigen discovery (selecting most suitable variants), validation of structural integrity and authenticity, engineering refinements to improve epitope presentation, mapping antibody epitopes, and choosing adjuvant formulations that are effective in preserving complex, conformational epitopes. We can obtain structural and compositional information for proteins, glycoproteins, membrane proteins and protein-formulations under a range of sample conditions. These approaches can be used to address questions and issues frequently faced in working with protein therapeutics such as:
- Has a vaccine immunogen adopted a native-like fold with proper epitope presentation? How well-ordered and stable is the immunogen?
- Does the antigen exhibit favorable solution behavior such as monodispersity and solubility, rather than forming heterogeneous aggregates?
- How do modifications, mutations or variants of an immunogen affect their stability, structure, epitope presentation and antigenicity? Can these changes be correlated with differences in immunogenicity?
- What post-translation modifications are observed and how do they affect epitope presentation, structure and stability?
- What are the epitopes for monoclonal antibodies against the antigen?