Comparative testing of Ag85 isoforms and consensus sequence optimisation for next-gen TB vaccines
Led by Dr Andy Tran (City St George’s, University of London, UK), with Prof Andrea Cooper (University of Leicester, UK), and Prof Rajko Reljic (City St George’s, University of London, UK)
Project Aim
Tuberculosis (TB) remains one of the world’s most pressing health issues, claiming more lives than any other single infectious disease each year. While there is currently one licensed vaccine for TB, the BCG vaccine is only partially effective, making it essential to find better alternatives to replace or “boost” BCG. One promising strategy involves creating subunit vaccines that train the immune system to target specific components of the TB bacteria. A family of protein targets, known as Ag85, consisting of three different versions (Ag85A, Ag85B, and Ag85C), has shown promise in TB vaccine development. While these Ag85 isoforms have been studied in many TB vaccine candidates, including some in human clinical trials, their ability to induce an immune response and effectiveness in protecting against TB relative to each other has not been investigated. Additionally, there is potential to enhance vaccine efficacy by combining key components of these isoforms into a single “comprehensive” protein, called “consensus Ag85” (cAg85). To test the performance of Ag85A, Ag85B, Ag85C and consensus Ag85 as TB vaccine antigens, I will produce these proteins in the lab and then use mouse models to evaluate their ability to induce an immune response. By exposing the Ag85-vaccinated mice to TB bacteria and measuring the resulting infection three weeks later, I can also determine which Ag85 protein is most effective at preventing disease.
This study will provide crucial insights into what makes a successful TB vaccine, helping to design better ones that save more lives. Ultimately, my goal is to develop vaccines that offer enhanced protection against this deadly disease.
