A Phase 1 study of a preventive HIV vaccine testing a novel delivery mechanism known as electroporation – the use of electrical pulses to increase the immune responses elicited by DNA vaccines – was recently completed in New York City. The results show that TriGrid™, a technology developed by Ichor Medical Systems, Inc., helped to enhance the immunogenicity of the vaccine tested. Compared to intramuscular injection, the conventional mode of delivery, electroporation significantly enhanced detectable immune responses to the DNA vaccine, known as ADVAX, which was tested in 40 healthy human volunteers. Initial results were presented at the end of October at the AIDS Vaccine Conference in Paris, France.
Conducted by Drs. Sandhya Vasan and David Ho of the Aaron Diamond AIDS Research Center (ADARC) at the Rockefeller University Hospital in New York City, with technical support from the International AIDS Vaccine Initiative (IAVI), this randomized, placebo-controlled trial is the first systematic evaluation of an HIV DNA vaccine delivered with electroporation ever conducted in healthy human volunteers. In addition to evaluating the safety and tolerability of the vaccine candidate, the clinical trial also assessed the frequency, magnitude and breadth of human immune responses to ADVAX, a DNA-based AIDS vaccine candidate.
“We are pleased to have worked with such prestigious collaborators to complete this important clinical study,” says Ichor’s CEO Robert Bernard, “and are hopeful that the results will prove to be an important step forward in the field of HIV vaccine development and for DNA vaccines more broadly.”
The experimental vaccine tested consists of circles of DNA, which carry genes for proteins that are found in HIV. The vaccine is intended to teach the immune system to recognize and destroy cells that have been infected with HIV. Years of research in animal models have shown that DNA injected directly into muscle is not efficiently taken up by cells, but electroporation – the formation of small pores in cell membranes in response to pulses of electricity – with the TriGrid™ technology enhances the vaccine uptake between 100 and 1000 times. Getting the vaccine efficiently into cells, where it can start producing the proteins it encodes, is a step of critical importance to their mechanism of action. Ichor’s technology helps to do just this.
“We are excited by these results. They have shown that we must pay close attention to how we are delivering DNA vaccine candidates, to ensure they have the maximum impact possible,” said Dr. Pat Fast, IAVI’s Chief Medical Officer.
A total of 40 subjects were enrolled in the study, which was designed to compare the safety, tolerability, and immune responses to ADVAX following administration via either the TriGrid™ delivery device or conventional intramuscular injection. A total of 24 volunteers received ADVAX at one of three dosage levels (0.2 mg, 1.0 mg or 4.0 mg) by electroporation, another eight by conventional intramuscular injection at the 4.0 mg dose level, and another eight were given a placebo via the TriGrid™ device.