MART · Mucosal antibody and B cell responses during Tuberculosis
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2021-03-01 → 2023-04-14
- EU contribution
- €203,149
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
Mucosal antibody and B cell responses during Tuberculosis
Tuberculosis (TB) is one of the world’s leading causes of death from any single infectious agent, killing up to 1.5 million people every year. This is because strains of the bacterium Mycobacterium tuberculosis (Mtb), which causes TB, are increasingly developing resistance against available antibiotic treatments, and the only available vaccine provides limited protection. In the absence of an effective vaccine, it is mainly impoverished people with little access to long, expensive treatments that continue to bear the brunt of disease. Hence, there is a great urgency to develop new vaccines. However, a critical barrier to the development of an effective TB vaccine is our incomplete understanding of what constitutes a protective immune response. In the case of other respiratory infections, such as Influenza or COVID-19, the protective immune response induced by vaccines partly rests on the induction of pathogen-specific antibodies. However, in the case of TB, scientists still do not know whether such protective antibodies exist at the site of infection (the lung). The goal of this project was to characterise antibody responses in the lung of mycobacteria-infected mice and humans, and to assess their relationship to protection versus disease. By combining a mouse infection model with a clinical study of TB patients with different grades of TB susceptibility, the results from this project provide a sound basis for the development of mucosal airway vaccines against TB.
Data: CORDIS, © European Union
Project objective
Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis (Mtb), kills up to 1.5 million people every year. Despite sustained scientific attention, there is no effective vaccine, multidrug-resistant Mtb strains are on the rise, and impoverished people with little access to long, expensive treatments continue to bear the brunt of disease. A critical barrier to the development of an effective TB vaccine is our incomplete understanding of what constitutes a protective immune response.Accumulating evidence suggests a role for B cells and antibodies in preventing and alleviating TB. Existing studies show that some Mtb-specific antibodies found in blood may confer protection against infection. However, whether such protective antibodies exist at the site of infection and in what quantity remains unknown. The goal of this project is to characterise antibody responses in the lung mucosa of mycobacteria-infected mice and humans, and to assess their relationship to protection versus disease. First, I will identify the antigenic targets of antibodies isolated from lung and lymphoid organs of infected mice by proteomics. Then I will use tetramer-based enrichment and single cell RNA sequencing to investigate the dynamics, transcriptional regulation and B cell receptor repertoires of lung-resident, antigen-specific B cells – the source of lung mucosal antibodies. Finally, I will translate these findings from the mouse model to humans, using bronchoalveolar lavage fluid from a clinical study of TB patients with different grades of TB susceptibility. This approach will allow me to assess the existence of these mucosal antibodies in humans and to investigate their function and protective potential. Combining the mouse infection model with this unique TB patient cohort represents a unique opportunity to address the impact of humoral immunity in the lung mucosa, thus providing a sound basis for the development of mucosal airway vaccines against TB.
Original text from CORDIS.
Participants
- UNIVERSITAT BASEL · BaselCoordinatorSwitzerland
Links
Data: CORDIS, © European Union