Burnet’s Viral Entry and Vaccines Group has initiated a vaccine research project for COVID-19.
Critical for vaccine engineering for COVID-19 is an ability to elicit protective immune responses that do not also generate antibodies that enhance infection via antibody dependent enhancement (ADE) or potentiate disease through other antibody mediated mechanisms.
Vaccine development for SARS was halted because vaccination with the SARS spike protein resulted in worse disease outcomes in animal models.
In addition, humans that died of SARS have been shown to elicit IgG specificities that alter macrophage/monocyte activation and cause severe lung disease.
Using structure guided design, our group has designed unique antigens that are aimed at generating neutralising antibodies (NAbs) that do not cause ADE.
The approach is informed by lessons learned in HIV antigen design, another class I fusion protein. Antigen structure will be examined by cryo-EM at Monash University.
An immunisation study will be conducted using five different antigens and we will quantify both the neutralising antibody response and the ability of IgG to enhance infection in newly established biological assays.
Our groups are among Australia’s leading teams that bring together skills in virology, immunology, protein engineering, expression, purification, analysis, structure-function studies and analysis of immune responses to antigens.
They have determined structures of HCV antigens with monoclonal antibodies and will apply their skills to COVID-19.
Stages of vaccine development: