AITHM Seminar - Prof Stefan Kaufmann

Where: Cairns A21.002 video linked to Townsville 39.252A

When: 16 August, 2:00pm - 3:00pm

“Immunity to tuberculosis: from bench to bed and back again”

Stefan H.E. Kaufmann, Max Planck Institute for Infection Biology, Berlin, Germany

Tuberculosis (TB) remains a major health threat with 9.6 million cases and 1.5 million deaths in 2014. In my talk I will present an update on our TB vaccine candidate VPM1002, which has completed a phase IIa trial in newborn in South Africa, is undergoing a phase IIb trial in HIV exposed neonates in South Africa and has been submitted for a phase III trial in adults in India. The vaccine VPM1002 is a recombinant BCG in which the urease C gene has been deleted and exchanged with the listeriolysin gene. I will explain recent findings and describe mechanisms underlying improved protection by this vaccine. I consider this an informative example of translational work from bench to bed.

Next I will summarize our most recent biomarker research that has led to a diagnostic point-of-care biosignature for TB, and our attempts to define a prognostic biosignature, which can prognose risk of TB. Several markers of high discriminatory power for TB were discovered with thus far unknown functions in pathogenesis.

In the third part of my talk I will describe a reverse translational approach in which we characterize biological functions of such biomarkers. These include miRNA 223 type I IFN and neutrophils. A major conclusion of this work reveals that neutrophils are detrimental in TB. First, because they cause tissue damage, and second, as myeloid-derived suppressor cells, they impair protective immunity.

In conclusion, I hope to convince the audience that a circle of translational and reverse translational research is most suitable to further our knowledge about pathogenesis of TB, and in parallel, to develop improved intervention measures for better control of this health threat.

Further reading:

1. D.E. Zak et al, Lancet 387:2312 (2016)
2. S.H.E. Kaufmann and A. Dorhoi, Immunity 44:476 (2016)
3. Maertzdorf et al., EMBO Mol. Med. 8:86 (2015)
4. Vogelzang et al., J. Infect. Dis. 210:1928 (2014)
5. Dorhoi et al., J. Clin. Invest. 123:4836 (2013)
6. Maertzdorf et al., Proc. Natl. Acad. Sci. 109:7853 (2012)
7. Knaul et al., Am. J. Resp. Crit. Care Med. 190:1053 (2014)
8. Dorhoi et al., Eur. J. Immunol. 44:2380 (2014)