The study in mice boosted the immune response by removing the host's natural immune "brake." By unleashing the immune system's full potential in conjunction with conventional antiretroviral treatment, HIV could be treated more effectively or prevented altogether.

"A lot of vaccines work very well in dealing with some pathogens, but for HIV, the natural immune response usually fails," said Dr. Si-Yi Chen, associate professor at the Center for Cell and Gene Therapy at BCM and senior author of the study. "The natural immune regulator may not allow the immune system to respond to HIV infection strongly enough. So by relieving the 'brake,' we can hopefully overcome what is failing in the natural anti-HIV immune response."

In the study, funded by the National Institutes of Health, Chen and colleagues examined a molecule, SOCS1, which regulates how antigens are handled by dendritic cells, specialized white blood cells that activate the immune system.

The researchers previously found that dendritic cells in which the SOCS1 was turned off were more efficient at stimulating the body's immune cells.

Most immunization attempts to stimulate an immune response to HIV in the past have been disappointing, but Chen says his laboratory results hold promise to make current HIV vaccines work better. SOCS1 was found to be part of a pathway that not only controls the production of compounds (cytokines) that stimulate inflammation but also plays a critical role in regulating the potency of anti-HIV immune response. Dendritic cells in which SOSC1 was switched off were able to induce an effective long-term memory immune response to HIV.

"In mice, we were pretty consistent in activating anti-HIV immune responses," said Chen. "In most cases, we found a significant enhancement in both antibody and T-cell response by inhibiting SOCS1."

Chen hopes this immunization approach of inhibiting SOCS1 will help develop more effective prophylactic as well as therapeutic vaccines. Therapeutic vaccines may contribute to the long-term control of HIV infection and will relieve HIV patients of their heavy dependence on antiretroviral drugs, many of which are expensive and require daily administration.

"Conventional wisdom is that natural immune responses play an important but insufficient role in controlling HIV infection," said Chen. "Hopefully this therapeutic vaccine can boost the natural immune responses strong enough so you don't have to take these anti-HIV drugs all the time."

Chen anticipates testing the HIV vaccine in humans in the next several years. He foresees the SOCS1 silencing strategy enhancing therapeutic and prophylactic vaccines against other pathogens in addition to HIV.

Drs. Xiao-Tong Song and Kevin Evel-Kabler, both postdoctoral associates at BCM's Center for Cell and Gene Therapy, also contributed to the study.

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