HIV

A high HIV mutation rate enables escape from powerful immune responses and anti-retroviral drugs. Reuben Harris of the University of Minnesota in the U.S. will test the hypothesis that HIV requires the human APOBEC3G protein to maintain a high mutation rate necessary for HIV survival. Inhibiting this protein may slow the mutation rate and make the virus more susceptible to immune responses.

Gadi Borkow of Cupron, Inc. in the U.S. will study the efficacy of using newly developed copper-oxide based filters that deactivate a wide range of viruses, including HIV-1, as a shield to enable HIV-infected mothers to breastfeed their infants without risking transmission of the virus.

Ruth Ruprecht of the Dana-Farber Cancer Institute in the U.S. will develop a new vaccine platform for HIV based on the hypothesis that immunodominant regions of the virus may be irrelevant to neutralizing the virus and also prevent access to neutralizing epitopes in conserved regions. The team will also use structural mimics of important epitopes in an effort to generate a strong, broadly neutralizing antibody response against these conversed sites.

HIV destroys helper T cells, which are essential to activation of B-cells. Irvin Chen of UCLA in the U.S. will utilize inducible pluripotent stem cell technology to generate a constant, self-renewing source of antigen-specific B-cells, which target conserved HIV epitopes to eliminate HIV-infected cells.

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.

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.

David Sokal of Family Health International in the U.S., with colleagues at Cambridge and Drexel Universities, will develop and test low-cost filters coated with safe microbicides that can be inserted into tips of nipple shields to prevent HIV transmission during breastfeeding.

For viral replication, HIV viruses are dependent upon proteins, called proteases, to appropriately cleave peptides and form functional viral particles. Craig Crews of Yale University in the U.S. will attempt to exploit these proteases by designing a drug that will cleave only to HIV protease and release a cytotoxin that results in programmed cell death.

To harness a woman's immune system to prevent HIV-1 infection, John Fahey and Charles Wira at Dartmouth Medical School in the U.S. will identify SERMs (selective estrogen receptor modulators) similar to those used for treating breast cancer and osteoporosis that can induce local immune protection in the reproductive tract against HIV without compromising normal reproductive function or increasing the risk of HIV infection.

Renjie Chang of Lavax, Inc. in the U.S. has developed a natural food substance that reduces HIV viruses in the mother's milk, and will test it along with scientists at University of Toledo for its ability to block HIV transmission from mothers to infants.