Infectious Disease

Ronald Quinn of Griffith University's Eskitis Institute in Australia and colleagues are seeking to discover chemical fragments drawn from a variety of natural sources that bind to proteins expressed by the malaria parasite in its latent stage and the tuberculosis microorganism. In their Phase I and Phase II research, the team is working on identifying compounds that target proteins involved in key metabolic and energy pathways of latency as the basis for new drug therapies.

Michael Lebens of the University of Gothenburg Institute for Vaccine Research in Sweden proposes to develop a new oral cholera vaccine using a single cholera strain that expresses antigens for both the Inaba and Ogawa serotypes and produces cholera toxin subunits that act as an adjuvant to stimulate mucosal immune activity. In this project's Phase I research, Lebens and his team successfully generated potential vaccine candidate strains that express both Ogawa and Inaba type antigens simultaneously.

Antibodies and the complement system work together to specifically detect and clear viruses, but they are circumvented by HIV, which hides itself and the cells it infects by hijacking host proteins such as CD59. Qigui Yu of Indiana University School of Medicine in U.S. will attempt to unmask HIV and HIV-infected cells and render them susceptible to antibody-complement attack. In this project’s Phase I research, Yu and his team identified a potent, specific, and non-toxic inhibitor of human CD59, which is used by HIV to escape destruction by antibody-complement attack.

Ofer Levy at Children’s Hospital Boston in the U.S. will determine whether synthetic molecules called imidazoquinolines activate newborns’ white blood cells, and could be used as candidate vaccine adjuvants to dramatically enhance immunization at birth. In this project’s Phase I research, Levy demonstrated that Toll-like Receptor-7 and -8 agonists are superior to agonists of other Toll-like receptors and to alum, an already approved vaccine adjuvant, in activating newborn immune responses in studies in vitro.

Existing malaria vector control methods (e.g. nets and insecticide sprays) primarily target mosquitoes that enter or attempt to enter human dwellings, yet mosquitoes also obtain significant proportions of essential resources outdoors. Fredros Okumu of Ifakara Health Institute in Tanzania and his co-investigators therefore proposed the use of strategically-located outdoor vector control devices. In this project's Phase I research, the team created new and easy-to-use outdoor methods for luring, trapping and killing mosquitoes, including major African malaria vectors.

Patrick Kiser of the University of Utah in the U.S. will design a vaginal gel that blocks HIV by becoming impermeable in response to the pH change induced by the presence of semen, and includes a polymer engineered to bind to HIV surface proteins to halt viral transport to susceptible tissues and HIV target cells. In this project's Phase I research, Kiser and his team engineered a synthetic polymer that has many of the properties of mucus, and demonstrated that the polymers slow or stops the movement of cells in the presence of semen.

Saurabh Gupta and Ron Weiss of Massachusetts Institute of Technology in the U.S. proposed creating sentinel cells that can detect the presence of a pathogen, report its identity with a biological signal, and secrete molecules to destroy it. This project's Phase I research demonstrated that commensal bacteria can be engineered to detect and specifically kill the model bacterial pathogen Pseudomonas aeruginosa.

Laurel Lagenaur and the team at Osel, Inc. in the U.S. will engineer a native human vaginal Lactobacillus to secrete a potent and broadly antiviral domain antibody fragment and evaluate the microbe’s ability to prevent HIV infection in the vaginal mucosa. In this project's Phase I research, Lagenaur's team examined levels of expression of HIV-neutralizing proteins by Lactobacillus. Recently several broadly neutralizing domain antibodies have been identified.

Philana Ling Lin of the University of Pittsburgh in the U.S. will use imaging technologies such as PET and CT scans to study the biological mechanisms related to the reactivation of latent tuberculosis to better understand the fundamental characteristics of reactivation, as well as provide insight about new ways to induce or limit reactivation of latent tuberculosis.

Manoj Duraisingh of the Harvard School of Public Health in the U.S. will use RNAi screening to identify critical determinants in human red blood cells (erythrocytes) that are required for invasion and growth of the malaria parasite, Plasmodium falciparum. In this project’s Phase I research, Duraisingh’s group developed a RNAi-based approach for genetic analysis of the erythrocyte in vitro, and demonstrated that the major surface protein Glycophorin A is required for efficient invasion by some strains of P. falciparum.