Oregon Health & Science University researchers have received a $25 million grant from the Bill & Melinda Gates Foundation to advance work on a promising vaccine candidate that may someday prevent or cure infection with HIV, the virus that causes AIDS.
The grant — awarded to a team of scientists at OHSU's Vaccine and Gene Therapy Institute led by Louis Picker, M.D. — is among the largest philanthropic grants OHSU has ever received.
“We are incredibly grateful for the Gates Foundation’s support,” said OHSU President Joe Robertson, M.D., M.B.A. “This is great news for OHSU but even better news for the fight against HIV and AIDS. Dr. Picker’s research is at the leading edge of a process that might eliminate HIV from humans. The support of the Gates Foundation adds momentum to this vitally important work.”
"I am humbled, yet incredibly excited by the confidence the Gates Foundation is showing in our work," said Picker, who is associate director of the Vaccine and Gene Therapy Institute and director of its vaccine development program. "This generous level of support is a game-changer in how we can make real progress to defeat HIV and AIDS.”
Last year, more than 35 million people throughout the world were living with HIV, the virus that causes AIDS, according to the World Health Organization. While the annual number of new HIV infections has declined in recent years, an estimated 2.1 million people were newly infected with the virus last year.
And while antiretroviral drug therapy has also steadily decreased the number of AIDS-related deaths in recent years, an estimated 1.5 million people still died from AIDS last year, according to the WHO.
The work of Picker and his colleagues focuses on a possible vaccine that shows promise in not only preventing the HIV virus from establishing infection in exposed, uninfected individuals, but also holds the hope of eliminating the virus from people who are already infected.
Picker and his colleagues published research in the journal Nature last year that detailed how their vaccine candidate protected monkeys given the simian immunodeficiency virus — or SIV, the non-human primate version of HIV. The vaccine stopped the infection from spreading and then cleared it from the bodies of half of the monkeys it was tested on.
"In effect, we helped better arm the hunters in the body to chase down and kill an elusive viral enemy," Picker said. "And we're quite confident that this vaccine approach can work exactly the same way against HIV in humans."
The National Institutes of Health cited Picker's research among its "promising medical advances" of 2013.
The Picker team's approach involves the use of cytomegalovirus, or CMV, a virus that is already carried by most humans and is generally harmless. The researchers discovered, as they reported in Nature, that engineering CMV to express SIV proteins had a unique effect. This modified version of CMV was able to generate and indefinitely maintain so-called "effector memory" T cells that target SIV and are capable of searching out and destroying SIV-infected cells.
T cells are a key component of the body's immune system, which fights off disease. But HIV and SIV are able to evade T cells elicited by conventional vaccines or SIV/HIV itself. The SIV-specific T cells elicited by the modified CMV vaccine were different. These T cells were able to arrest a highly pathogenic SIV very early during the course of infection in 50 percent of monkeys, and over time were able to eliminate all traces of SIV from the monkey’s bodies.
The Gates Foundation had already supported Picker's team, which includes VGTI scientists Scott Hansen, Ph.D., Klaus Frueh, Ph.D., Jay Nelson, Ph.D., Patrizia Caposio, Ph.D., Dan Streblow, Ph.D., Victor DeFilippis. Ph.D., and Michael Axthelm, DVM, Ph.D., with an $8 million grant in January 2012. That, along with NIH research funding, helped the lab make significant progress on its vaccine work.
The new grant will allow the Picker team to test the safety of a prototype human version of the vaccine in a phase I clinical trial in humans. It will also help the team develop an optimized version of the vaccine suitable for larger scale efficacy testing. Although the current grant will be primarily focused on a preventative vaccine for HIV/AIDS, the same technology will be applicable to a therapeutic vaccine designed to treat already HIV-infected individuals on antiretroviral therapy with the goal of curing these individuals.
"We're still probably eight to 10 years away from proving this vaccine works to prevent or cure HIV infection in humans," Picker said. "But this grant will allow us to transition from nonhuman primate models to clinical testing, a critical step in vaccine development. This important work could not happen without this remarkable investment from the Gates Foundation. I believe their grant will help us kill this disease for good."