Accelerating BCG Efficacy: Targeting Dendritic Cell Migration in Tuberculosis Immunization
Led by Dr Luciana Balboa (Instituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS), University of Buenos Aires, Buenos Aires, Argentina), with Prof Marcela Henao Tamayo (Colorado State University), and Dr Taru S Dutt (Colorado State University), and Dr Federico Blanco (Institute of Biotechnology-IABIMO, CICVyA, INTACONICET, Argentina), and Dr Fabiana Bigi (nstitute of Biotechnology-IABIMO, CICVyA, INTACONICET, Argentina)
Project Aim
Tuberculosis (TB) is the world's top infectious killer. Currently, we do not have any vaccines to effectively combat TB, which is caused by the pathogen named Mycobacterium tuberculosis. The only vaccine available in regions where TB is common is the Bacillus Calmette-Guérin (BCG) vaccine, which is a live attenuated vaccine. Unfortunately, its effectiveness varies significantly in adolescents and adults. Despite many attempts to enhance the strength and quality of the immune response triggered by BCG, achieving complete immunity has been challenging. One area that remains largely unexplored is the possibility of speeding up the transportation of BCG to lymph nodes, which is crucial for starting an effective immune response. Specialised immune cells called dendritic cells, are believed to play a key role in this process. Our research has shown that when dendritic cells change the way these cells use sugars for energy generation —controlled by a master protein called HIF1A—they can move more efficiently to the lymph nodes in response to M. tuberculosis.
In this proposal, we aim to enhance the movement of dendritic cells in mice by improving the activity of the master protein HIF1A axis during the BCG vaccination process. Our objective is to investigate how this adjustment affects the initiation of the specific immune response and the level of protection against M. tuberculosis. Additionally, we hope to gather preliminary data that could support further research and lead to new strategies for improving existing TB vaccine candidates. This may also enable us to identify new indicators of protection, such as how quickly the specific immune response is triggered. This project will be a collaboration between three different institutions in Argentina and USA and will be led by a female early to mid-career scientist in Argentina.
