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Reports of research work funded by grants prior to 2012

Malaghan Institute of Medical Research

Characterising protective CD4+ memory T cell subsets that mediate protection against Tuberculosis

JR Kirman

Mycobacterium tuberculosis kills more people worldwide than any other bacterial infection.  The World Health Organization estimates that every year >1 million people die from Tuberculosis (Tb), and ~9 million people are newly infected.  In New Zealand, on average, 1 person a day is diagnosed with Tb. The current vaccine, Bacille Calmette Guérin (BCG), fails to provide reliable protection, ranging in efficacy from –20% to 80% protection (depending on the study).  With the increasing incidence of multi-drug resistant and extreme drug-resistance strains there is a desperate need for a more effective vaccine against Tb.  Our failure to develop such a vaccine stems, in part, from a lack of understanding of the memory immune response required to combat infection.  To that end, the aim of the research undertaken is to characterise the CD4+ memory T cells that protect against Tb.

During my fellowship tenure, we have achieved the following:

*Identified that lung-resident memory T cells are necessary and sufficient for protection elicited by BCG vaccination.

*Identified a problem with a commonly used adoptive-transfer model that throws doubt on previous reports of the CD4 T cell subsets that contribute to protective memory against TB, and developed a new model in which to test the role of different CD4 T cell subsets.

*Shown that mucosal immunization with BCG elicits an improved immune response compared to conventional parenteral delivery.

*Shown that mycobacteria can be used to recruit inflammatory dendritic cells to a tumour site, and can prevent tumour growth and elicit a systemic anti-tumour response.

Characterising protective CD4+ memory T cell subsets that mediate protection against Tuberculosis

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