Fecha registrada: April 08 2020

Welcome to the first webinar in our four-part series on vaccine development. This instalment highlights the value of differential scanning calorimetry (DSC) as an insightful technique for structural characterization of a multi-domain protein antigen.

Protein structure is tightly linked to function. Detailed characterization of protein structure enables you to understand and control protein function. It is therefore among the activities central to academic and industrial research and development.

The use of ever-more structurally complex molecules warrants a growing requirement for complementary and orthogonal analytics to ensure data quality and the reliability of research. The ‘first principle’ nature and high resolution of DSC makes it a well-established technique for extended structural characterization and stability profiling of biomolecules and viruses in solution. Due to its direct readout, broad temperature range and sensitivity to thermally-induced unfolding, DSC is also used as the gold standard technique for validation of data from higher throughput thermal stability assays.

This webinar, by David Staunton, covers the basic principles of DSC and its application to the development of Neisseria meningitidis vaccine candidates.


Neisseria meningitidis is the leading cause of bacteraemia and sepsis in children and young adults due to the non-specific nature of its initial symptoms and the rapid progress of infection. Vaccination is the best approach to protect individuals and progress has been made in their development. However, the existing strategy cannot be used with serogroup B, which is the most common form of the disease in Europe and North America. 

An alternative vaccine candidate is the factor H binding protein (fHbp), a 27 kDa lipoprotein that can be divided into three variant groups, V1, V2, and V3, and which consists of two beta barrel modules. Members of the variant groups share 85% amino acid identity, but only 60-70% similarity between groups and immunization with only one variant generates immunological cross-reactivity within but not between variant groups. Efforts have been made to design functionally inactive but immunogenic fHbp as vaccine candidates. X-ray structures of V1 and V3 were obtained, but only the carboxy beta barrel module was observed for V2. Differential Scanning Calorimetry (DSC) was used to determine the folding stability of the fHbp variants to explain this observation. The advantages of applying DSC over other protein stability analyses will be discussed.