Can DNA therapeutic vaccines turn HIV+ patients into elite controllers?

Current_Research_and_Opinions_200The US federal Government spent $15,600,000,000 on providing it’s HIV positive citizens with antiretrovirals during the fiscal year of 2012. With many people living with HIV now surviving to near normal ages and the spread of the disease continuing, this ongoing cost will only grow annually. As ARV’s are a constant necessity for the 1.2 million HIV positive Americans, there is no predicted relief of the individual lifetime cost of $367,134.

Researchers are looking for new types of medications that will eliminate or partially eliminate the need for ongoing ARV treatment. However, research is being hindered and not by a lack of knowledge or ideas on how to slow the virus but by financial considerations. One such drug whose progress is being slowed is a therapeutic vaccine called GenePro (delta4SHIVku2).

As our understanding of the pathogenesis of HIV and the effects the virus has on the immune system has progressed through the years, so has and is the premise for the role of therapeutic vaccines.

A successful therapeutic vaccine is now thought to be one that produces a CD8+ memory cell response capable of killing infected cells and decreasing viral load to undetectable levels. Recent data aimed at eliciting a cure for HIV supports this hypothesis and the importance of CD8 cells, suggesting that a strong CD8 response is necessary in combination with awakening latent HIV in order to eliminate HIV reservoirs, highlighting the importance therapeutic vaccines may hold in maintaining viral clearance.

CD8 responses are believed to be lost in most HIV patients with the possible exception of elite responders. Elite responders (approximately 5% of people living with HIV) are able to maintain a suppressed viral load without the use of HIV antiretrovirals. Elite responders are able to maintain an undetectable viral load (below 50 copies/ml), sustain a CD4 count above 500 and do not experience symptoms related to HIV, for a period greater than 10 years, all in the absence of ARVs.

Research indicates that many elite controllers not only continue to possess CD8 cells after infection but that these cells have a superior capacity to proliferate. Although additional host restriction mechanisms appear to be necessary to elicit the viral control elite controllers possess, data indicates a strong CD8 response has been shown to be present in the majority of elite controllers and in many cases are a major factor in controlling viremia.

GenePro, made by a company named ImmunoGenetix, is a DNA based therapeutic vaccine, with a consistent lentiviral composition. This differentiates GenePro as it more closely mimics the virus, for appropriate immune responses. In mouse model and primates GenePro produced potent CD8 cells similar to those seen in elite controllers. These CD8 cells maintained HIV specific memory through out the life of the animals.

GenePro contains seven proteins which in vitro and animal studies show an ability to produce high levels of non-infectious proteins which elicits a much stronger immune response then other DNA vaccines that have been studied. GenePro stimulates a potent antibody response without the need for protein or viral vector boosts. GenePro doesn’t integrate into the genome host so there is no chance of mutations and it does not carry infectious virus. Electroporation is used to introduce it into the body, affording for superior infiltration into cells.

In a study of 19 macaques infected with SHIV, 12 primates where given injections of GenePro. The seven primates who did not receive GenePro developed progressive infection. The vaccinated macaques all achieved viral load decreases below the level of detection.

Cost is an important aspect of an effective therapeutic vaccine to ensure universal access. According to Dr. Mike McGrath MD. Ph.D, Professor of Laboratory Medicine, Medicine and Pathology at the University of California at San Francisco (UCSF) “Importantly, the cost of this approach is much less than one where the vaccine requires boosts with either recombinant viral proteins (expensive) or an infectious expression vector such as a pox virus or an adeno virus (more dangerous to health care and laboratory workers involved in utilizing these types of vector,etc).

Despite these positive results, funding for continued studies of GenePro has not surfaced, leaving the vaccine in the same position as many other potentially beneficial therapies not only in HIV but in all areas of medicine. Countless drugs have been delayed or lost due to difficulty finding the funds needed to continue into human clinical trials after successful animal studies. This conundrum has been dubbed ‘ The Valley of Death’ as scientists spend their time not producing data but in pursuit of money, often resulting in the loss of the drug.

In this case, the makers of GenePro were awarded $21 million dollars in NIH grants to develope and take the therapeutic vaccine to its present point. With invitro and animal study showing successful results, a strong CD8 response and viral load decrease to undetectable levels (the exact effect now thought to define a successful therapeutic vaccine) continued support from the NIH would be not only advantageous but is a practical utilization of scarce funds.

Without a system within the NIH that views potential research projects based on merit and results and which commits to assisting in taking a drug that shows extreme promise through development, countless drugs will continue to be lost. In the case of HIV, simple common sense dictates that funding a drug such as a therapeutic vaccine that shows potential in allowing for less use of ARV’s is not only an ethical and beneficial pursuit but is a common sense approach to tackling the growing cost of life long ARVs with a cost effective solution and is well worth the investment.

Written by Jeannie Wraight

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