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Next Generation Vaccine Development with Proteomics

Development of Universal Influenza Vaccines Understanding the sequence and structure of viral surface proteins allows innovative R&D for vaccine development. Computationally Optimized Broadly Reactive Antigens (COBRA) are being developed as universal vaccines against influenza by building a consensus sequence of the viral hemagglutinin (HA) proteins. There are 500 HA molecules on the surface of the virus that serve as the primary target for the antibody response. COBRA can be used across vaccine platforms including live viruses, mRNA, recombinant adenoviruses, split vaccines, etc. As nearly all individuals have pre-existing immunity to influenza viruses, influenza-specific memory B cells will likely be recalled upon COBRA HA vaccination. By comparing the antibody response towards specific wild-type influenza strains and COBRA antigens, we can begin to understand the potential for COBRA-based vaccines to be used in the clinic. Furthermore, if broadly neutralizing antibodies can be found against COBRAs, we can assess the potential utility of these antibodies for antiviral treatment of influenza. Proteomics in Influenza Studies Antibody binding performance can be assessed, followed by sequencing of antibodies of interest using Next Generation Protein Sequencing to enable recombinant production. When designing antibodies for research use or for potential therapeutic applications, it is important to understand where antibodies bind – antibodies in the repertoire may bind to the ‘head’ or ‘stem’ or both of the HA protein structure. For this purpose, HDX mass spectrometry epitope mapping can be used.