HIV

Ekaterina Dadachova of the Albert Einstein College of Medicine in the U.S., in collaboration with Arturo Casadevall, proposes to use radioimmunotherapy as a strategy to eliminate HIV-infected cells in patients on anti-retroviral therapy. Targeting viral antigens on these cells with radioactivity-armed antibodies could lead to HIV eradication. This project's Phase I research demonstrated that radioimmunotherapy can kill HIV-infected primary human cells in conjunction with anti-retroviral therapy (ART) and that this antibody can also reach HIV-infected cells in the central nervous system.

Roozbeh Ghaffari, Patrick Beattie, Jason Rolland and Jeff Carbeck of Diagnostics For All & MC10 Inc. will 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.

Because HIV infection activates naturally-dormant endogenous retroviruses (ERV) in human cells, Jonah Sacha will target T cells against these ERV antigens. Such targeting to eliminate HIV infected cells could be the basis for new host-directed vaccines. In this project's Phase I research, Sacha and collaborators demonstrated that ERV-specific antibodies are specifically triggered by infection with an exogenous retrovirus like SIV or HIV.

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.

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.

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.

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.

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.

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.

Keith Jerome of the University of Washington in the U.S. will utilize a class of proteins called homing endonucleases, which have the ability to cut DNA sequences, to target the DNA sequences unique to HIV, thus disabling the virus from making any more copies of itself. This project’s Phase I research demonstrated that homing endonucleases can find a model virus hidden in the genes of infected cells. In Phase II, Jerome’s team is now modifying these proteins in hopes of producing several that can specifically target and destroy HIV within infected cells.