Development of an RNA based vaccine against Mycobacterium tuberculosis
Led by Affiliate Prof Rhea Coler (Center for Global Infectious Disease Research, Seattle Children's Research Institute, USA), with Prof Helen Fletcher (LSHTM, UK)
Tuberculosis (TB) now ranks as the leading infectious killer worldwide, surpassing HIV/AIDS and malaria for the last several years in a row. The bacterium that causes TB disease, Mycobacterium tuberculosis (Mtb), is typically transmitted by inhaling the bacteria from infected people. These bacteria infect one-quarter of the world’s population, causing disease in ~10.4 million people and resulting in ~1.6 million deaths each year. Therefore, new TB vaccines represent a critical, unmet global public health need.
A new vaccine technology, based on the delivery of self-replicating RNA molecules, has gained attention worldwide but there has been limited exploration of this vaccine technology in protection against TB. IDRI has adapted their ID93 vaccine antigen into a self-replicating RNA molecule formulated in a state-of-the-art nanostructured lipid carrier. This enables the RNA vaccine candidate to be compared head-to-head with the classical ID93 protein with adjuvant vaccine, currently in phase 2b trials. Comparison of the nucleic acid based ID93 with the classical protein adjuvant formulation of ID93 will accelerate the development of the RNA based vaccine and provide insight into the breadth and magnitude of immune response induced by nucleic acid versus protein based vaccines.
We will evaluate ability of these vaccine candidates to reduce bacterial burden in the mouse model along with the accompanying immune responses. Recent clinical trial data have uncovered sets of host biomarkers that identify people who are more likely to advance to active disease states. This proposal aims to evaluate these clinically defined host markers (post-Mtb challenge) in a preclinical model of TB and to determine if immunization with two different types of vaccine candidates influences these host risk signatures. Successful completion of this proposal would significantly advance the TB vaccine pipeline and has the potential to streamline efforts and resources for the most promising candidates.