Exploring the Mycobacterium tuberculosis antigenome: New insights for the development of vaccines, diagnostics and drugs

Coppola, M. (2022)

Doctoral Thesis

Every day Tuberculosis (TB) kills approximately three thousand people, a number that is on the rise due to the impact of the current COVID-19 pandemic on essential TB services. The causative agent of TB, Mycobacterium tuberculosis (Mtb), is an ancient pathogen that through its evolution developed complex mechanisms to evade immune surveillance and acquired the ability to establish persistent infection in its hosts. To achieve TB eradication, the discovery of Mtb antigens that effectively correlate with the human response to infection, with the curative host response following TB treatment, and with natural as well as vaccine induced protection is critical. This thesis contributes to this ambitious aim through several findings. First, it uncovers multiple new in vivo expressed Mtb (IVE-TB) antigens by combining Mtb-transcriptomic data with advanced bioinformatics tools and medium throughput cytokine screening. Second, it deepens our understanding of the cellular and humoral immunity to Mtb antigens in latently Mtb infected donors (LTBIs) and TB patients as well as in animal models. Lastly, it demonstrates the feasibility of combining and integrating pre-clinical research of multiple mycobacterial diseases, which are endemic in the same areas and against which vaccines could induce cross-disease protection (i.e., TB and leprosy).

• Mycobacterium tuberculosis (MTB)
• Antigen discovery
• Therapy
• Transcriptomic
• Tuberculosis
• Leprosy
• Vaccine
• Cell responses
• Cytokines
• IgG

• All authors: Coppola, M.
• Supervisor: Ottenhoff, T.H.M.
• Co-supervisor: Geluk, A.
• Committee: Smits, H.H.; Visser, L.G.; Hiemstra, P.S.; Dockrell, H.M.; Stenger, S.
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2022-11-03
• ISBN (print): 9789464218770