Infectious Disease

Because human carriage of pneumococcus usually results in improved immunity to future infections without any development of disease, Stephen Gordon of the Liverpool School of Tropical Medicine in the United Kingdom will use an intranasal inoculation with a safe strain of the bacteria to study the mechanisms of mucosal immunity in the lungs and to explore the potential for a vaccine based on his findings.

Dennis Hartigan-O'Connor of the University of California at San Francisco in the U.S. will test whether expanding Th17 cell populations, a subset of CD4 T cells that protect the gastrointestinal tract against microbes, can augment the gut's general defenses and protect against the acute and chronic effects of HIV.

Kyu Rhee of Weill Cornell Medical College in the U.S. will test the theory that tuberculosis utilizes metabolosomes, which are protein-based metabolic structures, to enter into, maintain, and exit from latency. Understanding how metabolosomes work will aid in development of drugs that target TB.

Roozbeh Ghaffari, Patrick Beattie, Jason Rolland, and Jeff Carbeck of Diagnostics For All & MC10 Inc. in the U.S. sought to develop disposable paper-based diagnostics devices embedded with optoelectronics, allowing quantitative colorimetric analysis for HIV viral load monitoring. This platform addresses practical limitations of current image capture methodologies and eliminates the need for external readers.

Louis Schofield of The Walter and Eliza Hall Institute in Australia will develop a synthetic saccharide-conjugated vaccine that would provide immunity against GPI, a toxin produced by the malaria parasite that is a major determinant in the severity and fatality of the disease. This project’s Phase I research demonstrated preclinical safety and efficacy of a synthetic anti-toxin vaccine for malaria, showing that the oligosaccharide target was conserved across all malaria species and life stages.

Luke Savage and Dave Newman led engineers at Exeter University in the United Kingdom in a program to develop a handheld, inexpensive battery-powered instrument that can rapidly diagnose malaria. By using magneto-optics to detect the hemozoin crystals produced as a byproduct of malaria parasite digestion of hemoglobin in the red blood cell, they avoid relying on invasive blood sampling.

Because a robust immune response can actually foster HIV replication and spread, Joseph (Mike) McCune at the University of California at San Francisco in the U.S. proposed that building tolerance to HIV will hinder disease progression better than vaccinations that activate the immune system and trigger HIV activity. This project’s Phase I research demonstrated in a non-human primate model that tolerance to SIV could be induced by introducing SIV antigens to fetuses in utero.

Teun Bousema of Radboud University in the Netherlands proposed that geographic "hotspots" of malaria disease drive local transmission, and therefore that interventions would most efficiently be deployed if they targeted these hotspots. This project’s Phase I research demonstrated that hotspots of malaria transmission are present at all levels of endemicity and can be sensitively detected by serological markers of malaria exposure.

Carl Nathan and Gang Lin of Weill Cornell Medical College will test their hypothesis that tuberculosis is able to exit latency by distributing damaged proteins to a senescent cell lineage, while more functional proteins are diverted to a lineage with full replication potential. Regulating this post-latency cell division could be the target of novel drug therapies.

Jackie Obey of the University of Eastern Africa, Baraton in Kenya will test the efficacy of a diagnostic test for malaria in which small amounts of blood are mixed with an iron solution to create vibrant colors that indicate the amount of a protein released by the malaria parasite.