Rational design of synthetic vaccines against cancer and COVID-19

Abstract

The conception of modern vaccines has extended from medicines that prevent infectious diseases to therapeutic drugs for treating many diseases including cancers. Advancements in synthetic immunology have also allowed vaccine development to shift from empiricism to rational vaccine design based on epitopes, providing new hope for the development of vaccines against several major pathogens that cannot be treated with conventional strategies. The discovery and selection of epitopes are critical to rational vaccine design. Current methods for discovering epitopes include the analysis of clinical samples that can provide accurate results, whereas algorithm-based prediction can offer reliable prediction of outcomes in the future. In the current studies, we experimentally investigated epitopes of SARS-CoV-2 and then developed algorithms for the prediction of epitopes and their antigenicity. Together with my colleagues, I selected validated B cell epitopes to design a SARSCoV-2 vaccine. Similarly, the discovery and selection of T cell epitopes is important for vaccines against cancers. To elicit specific T cell responses, newly generated antigens (neoantigens) from tumour cells were selected as T cell epitopes. I then developed a self-adjuvanting self-assembling nanoparticle that mimics viral particles to optimise the T cell responses. I further investigated B cell responses provoked by this neoantigen vaccine.