OHSU Extra, Winter 2014
An AIDS vaccine candidate developed at OHSU may herald the end of an epidemic.
Last fall, Louis Picker, M.D., and his colleague, immunologist Scott Hansen, Ph.D., poured two sips from a bottle of scotch and raised their glasses for a toast. It’s a tradition the two friends observe only when they’ve made a fundamental discovery – and that day, they had reason to celebrate.
Picker and his team at OHSU’s Vaccine and Gene Therapy Institute had developed a vaccine candidate that has the ability to completely clear an AIDS-causing virus from the body.
“We’ve beaten the Death Star,” said Picker. “We’ve proven the principle. We’ve demonstrated that it’s possible to win against this virus.”
Their work has been published in the journal Nature and electrified this year’s International AIDS Conference. Most important, it offers new hope for the 34 million people worldwide who are infected with HIV today.
Tested in non-human primates at OHSU’s Oregon National Primate Research Center, the vaccine vanquished a particularly lethal form of SIV, the virus that causes AIDS in monkeys. Picker’s team vaccinated 16 monkeys and then infected them with SIV. In nine of the monkeys, the vaccine had a remarkable effect. It did not prevent initial infection, but it armed the body’s immune system to quickly overcome the virus. Within one to three years, there was no sign of infection – suggesting that the monkeys were cured.
The development is hailed as a major breakthrough. Never before has a vaccine eliminated an existing infection. “This is a first!” said leading HIV researcher David Watkins, Ph.D., professor and vice-chair of research at the University of Miami’s Miller School of Medicine.
The “just right” solution
How do you defeat a virus that mutates so quickly it has eluded all attempts at conventional vaccines? The key is a unique vaccine vector that Picker developed by retrofitting a common virus, called cytomegalovirus, or CMV, to contain SIV proteins.
Most people, and all adult monkeys, already carry CMV – a silent infection that typically causes no symptoms. Through thousands of years of co-evolution, humans and CMV have learned to
co-exist. This shared history makes CMV a “Goldilocks” vector, said Picker. It’s not too hot: it doesn’t trigger an overwhelming immune assault that would exhaust the immune system. It’s not too cold: its effectiveness doesn’t wane over time. It’s just right. The altered CMV equips the immune system’s T-cells to target SIV and stimulates them to patrol the body in a constant state of readiness.
“There’s a lot to be done to take this forward and see if it works in humans,” said Picker. The next step is clinical trials to test an HIV version of the vaccine in humans – a milestone that may take two or three years to reach.
Still unanswered is the question of why the vaccine did not work in half the monkeys. Perhaps combining Picker’s method with other approaches will increase the vaccine’s effectiveness. Or it may prove that although vaccines can improve the odds substantially, the virus could be too powerful to be beaten every time.
A life’s work, with lives in the balance
Even so, a significant reduction in AIDS cases would lead to millions of lives saved. Nowhere is that more true than in sub-Saharan Africa. Picker is well aware that advances made in Oregon have implications around the globe. His wife is South African and fought the spread of misinformation about AIDS through her work there as a journalist. Picker’s own career arc has tracked with the epidemic since he was in medical school. In the 1980s, Picker saw some of the first cases of AIDS treated at the University of California, San Francisco. As a pathology resident, he performed autopsies on some of its first victims. “As soon as I had some skills and understanding to make a difference, I began to work on this disease – and I’ve been working on it ever since,” Picker said.
The successful vaccine is the result of more than a decade of incremental progress. This leap forward has landed Picker in the spotlight, but he’s not comfortable lingering there for long. He has taken the time to field dozens of calls from reporters and to share the science at conferences. But from the moment he paused to toast this victory, Picker moved on to the next challenge. “All I can think about is what’s left to do,” he said. “There are questions left to answer, so I keep working.”
Picker believes his methods hold promise for new vaccines to protect against herpes viruses and cancers caused by viruses, such as cervical cancer. He is now developing vaccines for tuberculosis and malaria.
“Tuberculosis, AIDS, and malaria kill millions,” he said. “These are the three scourges of mankind.” With so many lives at stake, the immense promise of this research is coupled with intense pressure to move it forward quickly.
“I want to solve this problem in my lifetime,” Picker said. “We’ve made many new discoveries and crossed many hurdles, but it’s going to take a dozen fundamental discoveries before we’re done.” Picker is already in pursuit of the next breakthrough. He said, “Hopefully the scotch bottle will empty and the vaccine will be approved right around the same time.”
Promising vaccine moves toward clinical trials
The vaccine candidate that has eliminated an AIDS-causing virus in monkeys is proceeding toward clinical trials in humans. Philanthropy will play a key role in advancing this research on the fastest timeline possible – and in applying this OHSU breakthrough to new avenues in vaccine research.
“The biggest thing we have to do to keep this train rolling is not a scientific issue – it’s a financial one,” said Louis Picker, M.D., associate director of OHSU’s Vaccine and Gene Therapy Institute. “In these times, it’s difficult to raise the money needed for this research. I’m grateful for the support I have gotten from the Gates Foundation and the NIH, which has enabled us to come so far. But we’re probably going to run into trouble going forward unless we can find some additional support.”
Private philanthropy is essential for enabling researchers to pursue new ideas. “If you have momentum on an already established project, it’s possible to get federal funding for it,” said Picker. “What’s not possible anymore is the ability to try new things. If you have a new idea – in this case, to try to modify the vaccine for other diseases – that’s where philanthropy is needed.”
To find out how you can support vaccine development at OHSU’s Vaccine and Gene Therapy Institute, contact Lori Sweeney at 503 494-7455 or firstname.lastname@example.org.