Rafi Ahmed

Robert Koch Award 2017, together with Antonio Lanzavecchia

Rafi Ahmed will receive the Robert Koch Award for his pioneering studies on im-munological memory and T cell exhaustion, which have also proven highly fruitful for clinical research and treatment. His research centered on how memory cells can store an immune response for a practically unlimited time, once learned. Several of his papers were real game-changers, with Ahmed marking a radical departure from dogmas previously presumed to be reliable. For example, this is true of his proof that virus-specific memory CD8 T cells do not require a permanent stimulus with low quantities of corresponding antigens, as was believed until the mid-1990s. On the contrary, it is a property inherent in these cells themselves, which permits them to respond faster and more effectively on re-infection. Ahmed’s studies also defined long-lived plasma cells in the bone marrow that are responsible for maintaining antibody responses after infection or vaccination.

A milestone in Ahmed’s research was the discovery of T cell exhaustion during chronic viral infections and showing that the PD-1 inhibitory receptor is the major brake on these chronically stimulated T cells. It had long been known that chronic infections are associated with decreased T cell immunity and it was assumed that either the virus specific T cell responses were not generated or these T cells had been deleted. Ahmed’s studies showed that virus specific CD8 T cells were indeed present during chronic infection but their function was compromised. This finding suddenly presented the opportunity of breathing new life into these exhausted T cells and reviving their function. Ahmed then showed that exhausted CD8 T cells expressed high levels of the PD-1 inhibitory receptor and that in vivo blockade of this inhibitory pathway restores function in exhausted cells and results in viral control. This linking of T cell exhaustion with PD-1 has had a significant impact on the development of PD-1 directed immunotherapy for chronic infections and cancer.

PD-1 inhibitors have been clinically tested and are already approved for the treatment of several different cancers including lung, melanoma, bladder, etc. Rafi Ahmed believes that these new treatment strategies hold a lot of as yet untapped potential. His laboratory is currently seeking other factors that impede the immune system and is using a rational approach for combination therapy with PD-1 blockade including the use of therapeutic vaccines. While making his fundamental discoveries, Ahmed established one of the world’s largest vaccine research center at Emory University in Atlanta, which strives to find vaccines for HIV, hepatitis, tuberculosis, malaria and a universal flu vaccine, among others.

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