Mechanisms of antibody-mediated protection against tuberculosis.

Year of award: 2022


  • Dr Nyaradzai Sithole

    University of Cambridge, United Kingdom

Project summary

Almost all effective vaccines rely on antibody-mediated immunity. Despite increasing evidence that antibodies play a role in immunity to tuberculosis (TB), the current pipeline of TB vaccine candidates has focused on eliciting cellular immunity. One critical bottleneck that prevent maximising the utility of antibody-mediated immunity for novel TB vaccines is lack of understanding how antibodies protect against infection by M. tuberculosis (Mtb). To address the mechanisms of antibody-mediated immunity, our preliminary data supports a role for antibodies in stimulating inflammasome-mediated interleukin-1 release from Mtb-infected macrophages.

Using genetic and chemical tools, we will determine the mechanisms by which inflammasome stimulation mediates protection, both in vitro and in animal infection. Moreover, we have shown that protective antibodies alter the relative abundance and activation status of both innate and adaptive effector cells in the Mtb-infected murine lung. Using single-cell RNA sequencing, we will identify the cellular phenotypes and spatial organisation associated with antibody-mediated protection. Finally, I will investigate the role of activatory and inhibitory Fc receptor signalling in mediating antibody-mediated protection. Taken together, the proposed studies will help rationally improve future TB vaccines taking into consideration antibody-mediated immunity.