Vaccines & Immune Biology

Chang Liu and Xiaohong Kong of Nankai University in China seek to develop a self-destructive virus vector called HIVi, which will express small interfering RNA to silence HIV in infected cells, and also replicate in a controlled manner to outcompete the HIV infection before turning itself off. The efficacy of HIVi in interfering with HIV will be assessed using a number of standard HIV cell-based assays.

Firdausi Qadri of International Centre for Diarrhoeal Disease Research (ICDDR,B) in Bangladesh proposes that the presence of parasites in the guts of people who receive enteric vaccines diminishes the resulting immune response. Qadri hopes that by providing children with antihelminthic and anti-giardiasis drugs prior to administration of an oral typhoid vaccine, a robust immune response can be mounted.

Gregory Moseley, Stephen Rawlinson and David Jans at Monash University in Australia will engineer a live virus with a self-destruct sequence for use in a vaccine. This virus would be identical to a wild-type virus, but contain destabilizing domains fused to key proteins that can be regulated to first allow the virus to replicate and induce an immune response, and then be destroyed.

Jason Rasgon of the Johns Hopkins Bloomberg School of Public Health in the U.S. will engineer a virus to express a scorpion toxin that kills mosquitoes. After infecting mosquito larvae, the virus will express the killer gene when the insect becomes old enough to reproduce, but not old enough to transmit the malaria parasite. By allowing the mosquito to reproduce, the virus not only will be transmitted vertically to the next generation, but will also significantly slow the evolution of resistance to the gene.

Rong Fan of Yale University in the U.S. seeks to develop a microchip to assess the functioning of single T cells. If successful, this technology could be used to evaluate HIV-specific T cell response in future HIV vaccine trials.

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.

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.

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.

Benjamin Chain of University College London will attempt to stimulate an antibody response against CCR5, a protein found in the body which is used by HIV to infect cells. By combining a small portion of the molecule with part of the tetanus bacterium, Chain hopes to overcome natural tolerance of CCR5 to deplete the presence of the protein and prevent a way for HIV to enter cells.

Barry Peters of Kings College London will study the balance of tolerizing and stimulating immunity in HIV patients identified as "long-term non-progressors" in an effort to determine whether it is development of tolerance to HIV, and not immunity, which prevents the progression of the disease to AIDS.