New vaccine candidates found to control HIV progression

A new study by University of Toronto researchers has produced important findings on the control of HIV progression using new vaccine candidates.

The study, lead by Professor Kelly MacDonald of Mount Sinai Hospital and the Department of Medicine at U of T, looks at the effects of two vaccine candidates, Delta 5 and Delta 6, on the progression of simian immunodeficiency virus, the “monkey version” of HIV. The two vaccine candidates, developed in conjunction with Dr. Mark Wainberg of McGill University, are weakened forms of the HIV virus that contain only the structural proteins.

The initial testing of these weakened viruses on monkeys, however, produced unsatisfactory results. “We were disappointed,” MacDonald states, “because after we gave the monkeys these viruses we couldn’t find any ongoing evidence of replication, and we couldn’t measure their viral load at all.”

“The first thought we had was that they didn’t even replicate, that there was no effect,” continues MacDonald, “but when we actually measured the immune response in the monkeys against them we saw that their immune systems had made a very weak response to the proteins.”

MacDonald and team were unimpressed with these initial results and decided to package these weakened viruses as DNA immunizations, to see if it would be able to give an immune response that had a more significant protective value. They conducted these tests on monkeys again, giving them the weakened viruses as DNA vaccines. This time they received more encouraging results.

Scientific associate David Willer, who is also working on the project, explains, “We had two vaccine candidates that we were looking at and comparing to control animals. In one of the vaccine groups we had 100 per cent of the animals starting to control their viral load. In the other vaccine candidate group we had half of the animals control their viral load.”

This was quite an accomplishment for the project. Looking at those results alone, 75 per cent of the animals that were vaccinated, although they ultimately became infected, were able to control their viral load and maintain their immune status. “Something in the immune response that we elicited with our vaccines helped these animals maintain a more healthy disease and otherwise keep their disease in check for longer,” Willer states.

“This really was unexpected,” MacDonald says. “We were expecting that if the vaccine were to have any benefit, it would prevent infection. But where the vaccine did have its benefit was that these animals were infected but they did not show any signs of disease. The virus was there, but they were perfectly healthy.”

These weakened viruses as vaccines draws on the principle of triggering natural immunity to control HIV progression, something that is seen within the HIV-infected population. Five per cent of people who get infected with HIV are able to live quite well, keep their virus completely suppressed, and don’t require anti-viral drugs. “Also, 75 per cent of the monkeys that we tested were exhibiting this ability to control HIV progression, so we were quite amazed,” says MacDonald.

Willer also details how the HIV vaccine project is different from most vaccine approaches being researched and under trials at the moment. Most trials now rely on adenoviruses or pox viruses as the mechanism of delivery for the vaccine itself. With these viruses there is only a finite time in which the delivery mechanism presents an antigen (needed to stimulate antibody production in your body) before they’re completely cleared by the immune response. Willer explains that unlike current ongoing vaccine trials, his team mainly uses the Herpes viruses as the delivery mechanism.

“The biology of Herpes viruses is such that they get into your system, but they remain in a latent phase and every now and again they reactivate. They are able to potentially provide antigen presentation periodically throughout the life of the individual, and boosting the immune response every time they do so.” This unique characteristic of the Herpes viruses then provides a continuous immune response for the individual.

“Instead of a one-shot deal, which is the case with using adenoviruses or pox viruses,” Willer continues, “our approach hopes to take advantage of Herpes virus biology and provide more of a long-lived, durable immune response.”

Professor MacDonald and her group made many significant findings through this project, but there is still a lot of work ahead of them. “These viruses infect people differently at different levels, so there’s still a lot of tinkering that you need to do,” MacDonald says.

MacDonald and her group are currently preparing a team grant for future work on this project. This grant will seek to expand the project by bringing into the HIV vaccine area the expertise of other scientists at the university who are working in similar fields.