Vaccines & Immune Biology

To provoke an effective immune response against HIV, George Dickson of Royal Holloway -University of London will utilize HIV-based lentivectors encoded with a strong neutralizing epitope derived from tetanus toxin or influenza on its surface. By forcing production of such highly immunogenic and stable antigens, the immune system will respond with corresponding antibodies and control virus replication.

In pursuit of a new type of AIDS vaccine, Zhiwei Chen of the University of Hong Kong will work to use a variant of the primate CCR5 gene as an antigen and test its efficacy in inducing cross-neutralizing antibodies against this important HIV co-receptor.

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.

Marilia Cascalho of the University of Michigan will test whether a "mutable"DNA vaccine in which the gene coding for the antigen mutates a million times more frequently than a typical gene will trigger immune response that anticipates the production of new viral variants and produces broadly neutralizing antibodies against HIV.

To test the theory neutralizing antibodies can be "programmed" to recognize broadly divergent HIV envelope proteins, Nancy Haigwood of Oregon Health & Science University will work to design components of an HIV vaccine using groups of related envelope sequences.

Pandelakis Koni of the Medical College of Georgia will study the complex sugar coating that surrounds and protects HIV to see if parts of this shield can serve as targets for a vaccine, to generate antibodies that bind to and accelerate the killing of HIV-infected cells.

Douglas Nixon of the University of California at San Francisco will test his hypothesis that APOBEC proteins, which have been found to restrict replication of HIV, can be used to as an immunogen to stimulate a T cell response which would act against HIV infected cells.

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.

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.