HIV

Yue Chen of the University of Pittsburgh will attempt to develop an oral HIV vaccine based on Clostridium perfringens, a bacteria able to withstand upper GI conditions to deliver large amounts of antigens to gut-associated lymphoid tissue, a major site of HIV activity.

Johnny He of Indiana University proposes to engineer biodegradable nanoparticles that target active and latent HIV-infected cells by binding to the carbohydrate portion of the protein gp120, which the virus uses to seek out host cells. The "sticky" nanoparticles would then bind HIV, either in the blood, or within cells, killing the virus.

Using genome scans, Alfred Roca of the University of Illinois will test the possibility that isolated African populations have been repeatedly exposed to chimpanzee immunodeficiency viruses, and have evolved resistance to HIV. Ascertaining whether they display resistance to HIV could lead to new ways to fight HIV in other populations.

HIV has a very high rate of mutation allowing it to very rapidly develop resistance to AIDS therapies. The essential viral enzyme, HIV reverse transcriptase, lacks a "proofreading" or "repair activity" leading to errors or mutations. Karen Anderson of Yale University is working on "stealth" compounds that have a unique anchor specific for HIV. These compounds encourage the virus to make mutations until the virus is annihilated.

Dan Kaufman of the University of Minnesota will test whether natural killer cells, generated from stem cells can effectively target and eliminate HIV-infected cells.

Abraham Pinter of the University of Medicine and Dentistry of New Jersey will study the mechanisms that make neutralizing epitopes within conserved sites of the HIV virus resistant to antibodies, and will screen for reagents that can "unmask" these epitopes so that antibodies can target and eliminate the virus.

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.

Shi-hua Xiang of the Dana Farber Cancer Institute in the U.S. proposed engineering Lactobacillus, bacteria which normally reside in the human genital and gastrointestinal tract, to carry anti-HIV agents such as neutralizing antibodies, peptides, or other inhibitors. He and his colleagues hypothesized that introducing the engineered bacteria into the gastrointestinal tract would allow the bacteria to colonize and provide long-lasting protection against the virus.

While humans and chimpanzees share an overwhelming similarity between genes, primates exhibit a resistance to AIDS. Walter Messier of biotechnology company Evolutionary Genomics in the U.S. will research the mechanisms of eight genes that have adapted in chimps to identify how viral suppression works.

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.