PhD student looks for other ways to administer vaccines
By Trevor Pritchard
You're sitting on a bench in the doctor's office. The doctor pulls out a long, sharp needle that glimmers menacingly in the fluorescent light. Rolling up your sleeve, the doctor intones, "Hold still ... this might hurt a little."
If you're cringing while reading the above scenario, take comfort: Shawn Babiuk is trying to determine the effectiveness of alternate vaccine delivery methods.
Vaccines currently come in a number of guises, explains Babiuk, a graduate student with the Department of Pharmacy and Nutrition. Most people have had to swallow foul-tasting oral vaccines as children, and many are painfully familiar with the injections required to stave off diseases like tetanus and hepatitis. But vaccines of the future, hopes Babiuk, may be much less invasive than existing procedures - likely "as simple as rubbing a cream on the skin."
For the first part of his two-pronged PhD project, Babiuk investigated the feasibility of using topical vaccines - vaccines applied to the skin's surface - to protect the body from harmful viral invaders. The topical vaccines he employed in his project were composed of DNA plasmids delivered in liposomes, lipid complexes which increase the permeability of the body's cells.
"DNA vaccines were discovered about 10 years ago," says Babiuk. It was demonstrated that injecting plasmids - the circular DNA that encodes genes - into animals could induce immune responses to the coded gene.
Combining the plasmids in water with liposomes, Babiuk created a cream that permitted the vaccine's absorption into the body through the skin. "We wanted to see if we could induce immune responses by topically applying plasmids in liposomes," explains Babiuk. Since liposomes allow the vaccine to penetrate both the skin and the cell membrane, the vaccine could be administered without breaking the skin's surface with a needle.
Unfortunately, Babiuk's results were not as promising as he had originally hoped. "We were able to induce some immune response topically," he explains, "however [topical vaccines] are currently not as effective as conventional injections."
Babiuk then focused his attention on enhancing the delivery methods of injected DNA vaccines. The foremost problem with DNA vaccines of all types, says Babiuk, occurs with what immunologists term gene expression - the production of a protein from the information on the DNA.
It's a process that he describes as largely hit-and-miss. "You inject billions of plasmids, but only a few hundred enter cells and produce the encoded antigen."
In order to amplify the chances of causing an immune response, Babiuk administered short 200-volt pulses of electric current simultaneously with the injection. The process, known as electroporation, was intended to have a similar effect on injected vaccines as the liposomes had upon topical vaccines: enhancing the cell's uptake of the plasmid and thus transmitting the vaccine more efficiently into the body.
And his work with electroporation turned out to be quite promising. Says Babiuk, "We found out that electroporation can induce gene expression and also enhance immune responses."
Cancer patients, because of the high doses of medication they normally require, are most likely to benefit from Babiuk's electroporation research. "If you can deliver the drug intercellularly into the tumour [with the help of electroporation]," he explains, "you can kill the tumour and have fewer side effects."
Babiuk admits that inducing a potent immune response with a non-invasive procedure is the next obstacle to overcome. "What we want is to have effective vaccines that are the least invasive," says Babiuk. "The ideal situation would be to have a non-invasive delivery method which induces strong immune responses. However, my research has indicated that although we can induce strong immune responses, they [occur] only with highly invasive procedures."
Yet all is not lost for needle-loathers. Part of Babiuk's research explored the potential for electroporation-aided injections to deliver more than one vaccine with the same shot. He combined proteins from Bovine Herpes Virus and Hepatitis B into one solution, and was able to generate immune responses to both vaccines, an encouraging development.
"If we can theoretically deliver all your vaccines at once," he concludes, "maybe we can get away with a more invasive procedure."