Muscle cells: electricity makes their membranes briefly permeable

Wikipedia/Department of Histology, Jagiellonian University Medical College

[PARIS] A new way of delivering DNA vaccines could result in cheaper and more effective protection against HIV and other viruses, an international AIDS conference has heard.

DNA vaccines are made up of rings of genetic material into which genes from the disease-causing microbe are inserted. Once in the human cell, these genes induce the cell's machinery to produce microbe proteins that trigger an immune response.

Scientists presenting research at the Aids Vaccine 2009 conference in Paris this week (19–22 October) said that using an electrical field to enhance vaccine delivery boosts the effectiveness of DNA vaccines, which have so far had limited success.

The US team used — for the first time in healthy volunteers — electroporation, which applies an external electrical field to cells to temporarily increase the permeability of their membranes and let the DNA vaccine in.

Compared with vaccines that use a virus to smuggle the genes into the cell, a DNA vaccine is "easier to make, cheaper and more stable in high temperatures, thus very useful for the developing world", Sandhya Vasan, of the US-based Aaron Diamond Aids Research Center, told SciDev.Net.

But their impact has been limited, said Vasan, because the usual delivery devices, such as injection into muscle, are not successful at getting the vaccine into cells.

Her team analysed the safety and tolerability of electroporation, as well as determining whether delivering a DNA vaccine in this way resulted in a higher immune response.

They used a vaccine called ADVAX, made up of HIV-1 genes — which in previous studies had only induced a low immune response — and delivered it via a 'gun' that simultaneously injects the vaccine and an electrical charge.

The phase I trial involved 40 healthy volunteers who were split into groups to compare the immune response induced by delivering a placebo and different vaccine doses with either electroporation or injection alone.

"The results indicated that electroporation is safe, tolerable and efficient in improving cellular immune responses to a DNA-based vaccine," said Vasan. She added that no adverse events have been observed to date.

Nina Russell, senior programme officer for HIV vaccines at the Bill and Melinda Gates Foundation, says that the tolerability of electroporation is controversial.

"Some people argue that, as it implies electric charges in the human muscle to disrupt the cell membrane, it will be too painful," she explains.

Electroporation takes 3–4 seconds and the sensation is similar to a punch in the arm. Vasan, who has tested the system on herself, said that volunteers find it tolerable.