Preventing HIV Backwards

Given the body’s apparent inability to arm itself against HIV, this project is aimed at producing a vaccine that would prime the immune system, preparing it to target and kill HIV-infected cells. The novelty of this vaccine is that it will not be composed from elements of the virus, but rather, from the aberrant proteins the infected host cell makes in response to HIV infection. Instead of targeting the bewildering array of HIV viral strains produced by the virus’ relentless mutation, this approach attempts to immunize against stable, unchanging proteins symptomatic of cellular infection—a notable break from existing dogma.

Preventing HIV Backwards, as the innovative technique is known, is the brainchild of Stephen Johnston, researcher and director of Biodesign’s Center for Innovations in Medicine. His work investigates HIV’s possible links to deficient protein synthesis in infected cells.  Such understanding could be used to help marshal the assistance of normal human T cells to pinpoint infected cells (based on these aberrant host antigens) and destroy them. Thus, a resulting vaccine candidate would involve T-cell immunity, though of a qualitatively different type than involved in the virus-directed vaccines investigated thus far.

Experimental vaccine efforts to date have made use of the HIV genome or proteome (or components thereof).  While such an approach has been successful for many other viruses, including hepatitis B, it has thoroughly failed in the case of HIV, which may be a consequence of the virus disabling or destroying the very immune cells required to combat it. Given the apparent ineffectiveness in halting the HIV onslaught by pre-arming the immune system with HIV viral components, the time is ripe for a thoroughly new approach.

The concept of enlisting aberrant proteins to identify affected cells is also under investigation in the case of cancer, where the release of tumor-specific proteins could provide a target for a future vaccine.

 
Funded with support from: The Bill and Melinda Gates Foundation "Grand Challenges Exploration" grant