Seminario del Departamento de Química Biológica

Título de la presentación: Immunogen design to enhance stability and efficacy of viral vaccines 

Resumen: Most current viral vaccine formulations, including for COVID-19, require low temperature storage. This is a major impediment to widespread deployment, and contributed to the highly skewed distribution of vaccines, worldwide. Despite recent advances in the use of AI/ML for protein structure prediction and design, prediction of stabilizing mutations for complex, hetero-oligomeric proteins remains challenging. We have developed general methodology to both rapidly isolate stabilized protein variants and map their corresponding conformational epitopes in polyclonal sera. The workflow has been applied to identify thermostable Receptor Binding Protein (RBD) derivatives of the Spike protein of SARS-CoV-2 and other sarbecoviruses. These display enhanced yield and immunogenicity relative to both the corresponding wild-type RBD and Spike ectodomains. Several of these formulations can be stored at 37°C for several weeks without loss of antigenicity or protective efficacy. Using related approaches, we have developed multiple influenza vaccine formulations to protect against seasonal and pandemic influenza.  One of these has been shown to be safe and well tolerated in a Phase 1 clinical trial in Australia and further clinical development in India is ongoing.