Medicine
Strategy Is Developed to Fortify DNA Vaccine Against the AIDS Virus
Norman Letvin (left) and Dan Barouch.
Because the majority of new cases of HIV infection and AIDS are in regions of the world that costly drug treatments will never reach, developing an HIV vaccine has become a priority for curbing the pandemic. Norman Letvin, HMS professor of medicine at Beth Israel Deaconess Medical Center, and Dan Barouch, clinical fellow in medicine at Massachusetts General Hospital, have been working to improve naked DNA vaccines for HIV, a relatively new technology that shows promise but has not provided protection from infection in animal models. In results published in the April 11 Proceedings of the National Academy of Sciences, they have shown that immune responses to the DNA vaccine can be boosted significantly using a dose of the bodyÕs own immunological weapons.
These days, researchers have to understand which components of the immune response protect against infection. "With HIV, we are now faced with a unique paradigm for vaccine development," says Letvin. Recent research suggests that an HIV vaccine must elicit a broad range of immunity, incorporating both cytotoxic T lymphocytes and antibodies.
Naked DNA vaccines are a recent innovation, brought about by the discovery that a fragment of DNA encoding a viral gene, when injected into muscle cells, will churn out the protein it encodes. This protein production can generate a broad immune response without the need for a potentially dangerous vaccine made from a live though weakened virus.
Letvin and Barouch wanted to improve the existing DNA vaccine by harnessing a component of the immune system to nudge the immune response along. The augmented vaccine would provide HIV proteins for the immune system to attack while also supplying the weapons to make the attack more effective. They chose to use interleukin-2/Ig, a protein that fuses a T cell growth factor with a portion of an antibody molecule. By giving interleukin-2/Ig with the vaccine in an animal model, they were able to improve antibody responses about 30-fold and T lymphocyte responses about fivefold.
FULL STORY
