The devastating effects of the HIV pandemic will most likely be controlled only when a vaccine is developed that is safe and effective. Although a large number of vaccine trials have been conducted, all have demonstrated a complete lack of efficacy. The focus of Dr. Walker's laboratory is on a small minority of patients known as controllers of HIV infection. Those are patients who are infected with HIV, but in whom the disease does not progress.
The key difference observed in such patients with a natural protection against HIV progression is a broadly directed and robust T-helper cell response. This response is also detected in patients treated early in HIV infection but is rarely, if ever, detected in patients with more advanced HIV disease. "This indicates that vaccination strategies designed to stimulate T-helper responses may help prevent infection or possibly limit disease progression," said Dr. Walker. Dr. Walker's lab has identified a number of MHC class II epitope peptides that are broadly recognized by HIV infected patients and have the potential to induce a T-helper response similar to that observed in patients who resist the disease.
The classical problem in T-helper stimulation has been low affinity of epitopes to MHC class II molecules, which present the epitopes to T-helper cells. The solution to this problem, discovered and patented by Antigen Express scientists, is to modify the peptide epitope vaccine in manner that it bypasses the normal processing pathway for epitopes and interacts directly with MHC class II molecules. Specifically, a site was discovered on MHC class II molecules that controls the exchange of peptides at the antigenic peptide-binding trough of the molecule. Antigen Express scientists found that portions of a naturally occurring protein (the Ii-Key peptide) interact strongly with that site. Linking this Ii-Key peptide to an MHC class II epitope results in 200 times more effective presentation to T-helper cells than occurs using the epitope-only peptide. There is a 4-6 fold enhancement of T-helper stimulation in animal vaccination models.
"We are excited at initiating this collaboration in the field of HIV," said Dr. Eric von Hofe, vice president of technology development at Antigen Express. "Thanks to the work of Dr. Walker, the recognition of the importance of T-helper stimulation in the development of anti-viral therapies has begun to be widely accepted, as it has been in the field of oncology."
Studies are currently underway in Dr. Walker's lab to test the Ii-key/HIV MHC II epitope hybrids in using immunological assays specific for T-helper cells. Success in these studies will be followed by the addition of Ii-key/HIV MHC II epitope hybrids to HIV vaccine trials.
"We believe that this collaboration, with one of the foremost authorities on HIV vaccine development, is ideal to advance our technologies into an area that is desperately in need of novel strategies," said Anna Gluskin, CEO of Generex. "Dr. Walker has made notable contributions to the field of HIV research and has shown the importance of T-helper stimulation, an area of clear synergy with our colleagues at Antigen Express."
Source: Generex Biotechnology Corporation