Naomi Daniels Poster 2024

Dr Naomi Daniels

University of Otago, New Zealand

Evasion of BCG-mediated Immune Protection by Hypervirulent Strains of Mycobacterium tuberculosis

Poster Abstract

Tuberculosis (TB), a pulmonary disease caused by Mycobacterium tuberculosis (Mtb), kills more people every year than any other single bacterial agent. Some Mtb strains display selective advantages over other genotypes. In particular, Lineage 2-Beijing genotype Mtb strains exhibit greater virulence, a higher capacity to withstand treatment, and increased relapse after treatment. Beijing strains- which predominate in parts of East Asia- are associated with large TB outbreaks and multidrug-resistance. 
 
Despite widespread use of the TB vaccine bacillus Calmette–Guérin (BCG), protection is only achieved in ~50% of cases; alarmingly, BCG-mediated protection against Beijing strains is nonexistent. In a case contact study in Indonesia, although BCG protected contacts exposed to non-Beijing strains, there was no evidence of protection in contacts exposed to a Beijing strain. Similarly, in mice, BCG’s protection is diminished against Beijing strains. Our research seeks to understand why BCG fails to protect against Beijing-Mtb. We established an in vivo infection model utilising transformed clinical strains of Beijing- and control-Mtb with fluorescent tags to enable in vivo tracking. Early phagocytic responses and functional parameters were evaluated to assess whether Beijing Mtb subverts the antimicrobial activity of BCG-trained innate lung cells.
 
Furthermore, we investigated whether alternate vaccine delivery routes improved the effectiveness of BCG against Beijing Mtb. Using spectral flow cytometry and spatial transcriptomics we investigated whether Lineage 2-Beijing Mtb strains interact with different immune cells than control Lineage 4-Mtb strains; where infected and non-infected immune cells are located in the lung; how BCG-vaccination affects the location of Mtb; strain-related effects on immune cell gene expression in the context of the specific spatial location within the lung tissue microenvironment.   These data will inform design of secondary endpoints to be measured in an Indonesia-based clinical study of TB-exposed case contacts to improve TB vaccine function against Beijing Mtb. 

Biography

Naomi completed her PhD at the Malaghan Institute of Medical Research, Wellington, New Zealand. Presently a Postdoctoral Research Fellow at the University of Otago in Dunedin, New Zealand, Naomi's research centres on unraveling the mechanisms employed by highly virulent strains of Mycobacterium tuberculosis to evade protective immunity induced by the BCG vaccine. Specifically, this work focuses on determining the role of the innate immune system in the anti-mycobacterial response and ultimately aims to improve protective outcomes for novel TB vaccines.