TORONTO - Canadian researchers have been given the green light for human testing of an experimental HIV vaccine, but the initial trial will determine only its safety, not whether the vaccine works to prevent infection with the virus.
The U.S. Food and Drug Administration granted approval for researchers at the University of Western Ontario to test the vaccine, which is based on a genetically modified killed whole virus.
The SAV001 vaccine, developed by the lab of Dr. Chil-Yong Kang with financial support from Sumagen Canada, has been shown to stimulate a strong immune response in preliminary toxicology tests.
"FDA approval for human clinical trials is an extremely significant milestone for our vaccine, which has the potential to save the lives of millions of people around the world by preventing HIV infection," suggested Kang, whose research lab has spent the last 10 years developing the vaccine at a cost of about $10 million.
Kang said his team decided to seek FDA approval for the Phase I clinical trial because testing will be done in the United States, where the candidate vaccine is being produced. He said the stringent requirements of the U.S. regulatory body would also make it easier to seek approval for widespread commercialization of the vaccine in other countries in the future.
To make the vaccine, the researchers start by altering the genetic makeup of the human immunodeficiency virus to make it non-pathogenic — in other words, incapable of causing disease —then further inactivate it with chemicals and radiation.
"We have to make sure the virus is completely safe," Kang said Tuesday from London, Ont.
In Phase I of the clinical trial, set to begin in January, 40 HIV-positive volunteers will be injected with the vaccine to see if they suffer any dangerous side-effects.
If the SAV001 vaccine is found to be safe, it would require two more clinical trials that prove it works before it could be brought to market. Kang estimates it will cost another $100 million to complete those two trials.
"So as long as it doesn't show adverse effects, then we can go on for Phase II human clinical trials, that is to look at the immune responses and see whether they make antibodies against the virus," said Kang, explaining that testing would be performed in about 600 subjects who are HIV-negative but whose lifestyle puts them at high risk of becoming infected.
Phase III would test the effectiveness of the vaccine in a larger group of similarly at-risk individuals. Researchers hope to recruit about 6,000 high-risk volunteers for that final phase of testing, half of whom would be vaccinated and half left unvaccinated.
Kang said participants would be tracked for about three years to see how many in each group become infected with HIV.
"Suppose you have one or two infected individuals from the vaccinated group and then 200 or more from the non-vaccinated group, then you have efficacy," he said. "And that's how we calculate effectiveness of this virus vaccine."
Dr. Alan Bernstein, former executive director of the Global HIV Vaccine Enterprise, said it's important for the public to realize that the vaccine first needs to pass critical testing to make sure it does no harm.
"The only goal of any Phase I trial is to establish safety, so we will not know whether the vaccine is effective in preventing AIDS," said Bernstein, now a visiting professor at St. Michael's Hospital in Toronto. "This will not be a trial that says, 'We've got a vaccine now, guys,' even if it ultimately is."
The SAV001 is not the first experimental HIV vaccine to show promise in pre-clinical testing. A few others have reached this stage and gone beyond, only to fall short in the final analysis.
One of them was a Merck vaccine being tested in the STEP trial, which enrolled 3,000 international participants. The Phase II trial was halted when it found that more subjects who had been vaccinated became infected with HIV than those who received a sham vaccination.
Two years ago, an experimental vaccine studied in a large number of people in Thailand was found to protect against HIV infection in just under a third of those who received it. But the percentage wasn't high enough for researchers to conclude that the vaccine worked, so they are back in the lab trying to improve it.
Developing a vaccine against HIV has been a daunting task for scientists because of the complexity of the virus and the fact that it mutates so quickly.
There are seven major sub-strains of HIV, but the virus can mutate even as it is transmitted from one person to another, then mutate further to escape the infected person's own immune response.
"It's very hard to make one vaccine that can effectively neutralize all the different HIV strains that are found around the world or even amongst individuals in the same city," Bernstein said.
HIV is also a retrovirus, meaning it integrates its own genetic material into the chromosomes of key cells within the body, creating a latent infection that is extremely difficult to eliminate. To be truly preventive, a vaccine would need to be able to stamp out the virus before it reached that point, he said.
Scientists, wary of using a whole-virus vaccine because of the fears it might be able to cause infection, have tried using bits of the virus or genetically altered virus as a basis for their vaccines.
But Kang is confident that using the whole virus — albeit one that's been triply inactivated — may make his more efficacious in preventing HIV infection.
"I feel that I have a better chance to have this vaccine work because it has demonstrated that this strategy works for polio, hepatitis A, flu virus, rabies virus, and Japanese encephalitis," he said. "And there are 16 other animal virus vaccines using the killed whole virus strategy. They work to prevent infection."
Bernstein said it's important for scientists to keep testing different concepts in a bid to come up with a successful vaccine against HIV, which has killed 28 million people worldwide and infected another 35 million.
"I think what's interesting about this study is it's taking a very different approach. And diversity of approaches in science is key, is critical, because we don't know the right approach."