After years of research, a promising HIV/AIDS vaccine at the University of Maryland School of Medicine is moving into the critical human testing stage.
The school's Institute of Human Virology, headed by Dr. Robert Gallo, who helped discover the human immunodeficiency virus that causes AIDS and who developed the HIV blood test, announced the next big step in the research Thursday.
Scientists at the institute began work on the AIDS vaccine nearly two decades ago and have seen major breakthroughs on tests using animals, but, like much of the work on AIDS vaccines around the country, it has been a long process.
"The results in monkeys are interesting, but they're not perfect," Gallo said at an event at the institute's Baltimore headquarters to announce the human trial. "If we keep just using monkeys, we're never going anywhere. We need for humans to respond."
The institute's vaccine is just one of about 30 such drugs in some stage of human trials, according to AVAC, an advocacy group devoted to HIV prevention efforts. Since the first HIV vaccine trial opened in 1987, researchers have studied more than 50 candidates in more than 100 clinical trials funded by the National Institute of Allergy and Infectious Diseases.
A study conducted in 2009 in Thailand is the only one ever to show some promise, protecting about a third of patients against infection — not enough to support general use.
Even if it proves safe and effective, approval of the institute's vaccine by the Food and Drug Administration remains years away and would require several more rounds of increasingly complex human trials.
The initial phase the institute is entering this month is designed to make sure the drug is safe for patients and will take about a year. Later phases would test whether the vaccine performs as intended and include more patients than earlier stages. They also would take longer to help ensure there is enough data to support an FDA license.
For now, in what the FDA calls a Phase I trial, the institute will enroll 60 people; initially, 20 will get the drug.
Those who follow the field say the search for a vaccine for HIV/AIDS has become more diversified over the years as researchers are looking at a larger variety of ways to prevent the infection.
"The field is in an exciting place because it is trying a lot of different approaches," said Mitchell Warren, executive director of AVAC. "Sadly, in 30 years we still don't know what it will take to treat it. But we certainly have better ideas of what the answers to those questions might be."
An HIV vaccine has proved elusive for researchers in part because the virus attacks the body's immune system, which is needed to fight off viruses. Because no one has ever recovered from the disease — though many now can live long lives with it — scientists also have no human model of recovery to work from, according to the National Institute of Allergy and Infectious Diseases.
Scientists have long been frustrated by the ability of the AIDS virus to mutate and evade the immune system. The virus constantly changes the makeup of the proteins on its surface, making it difficult for antibodies to attack it.
Many other vaccine candidates have protected only against a narrow range of strains, researchers have said.
The institute's HIV vaccine targets parts of the surface proteins that the virus tries to hide. These parts are common in all strains of HIV. The virus only exposes them when it attacks a healthy cell.
It is hoped the antibodies produced by the new vaccine will bind to these parts and prevent infection.
"Our HIV/AIDS vaccine candidate is designed to bind to the virus at the moment of infection, when many different strains of HIV found around the world can be neutralized," Gallo said. "We believe this mechanism is a major prerequisite for an effective HIV preventive vaccine."
The institute's research on this vaccine candidate is being funded in part by $23.4 million given by a consortium led by the Bill & Melinda Gates Foundation, which declined to comment on the advance to a human trial. The U.S. Military HIV Research Program at the Walter Reed Army Institute of Research is also providing funding.
"It is a long road from concept to first in human studies and we are very pleased that our colleagues at IHV have navigated that road successfully," said Dr. Julie Ake, principal deputy director of the military program, of the institute's next step.
"We are looking forward to be able to one day combine it with other products we are developing," she said.
Medications now enable people living with HIV and AIDS to manage the disease and survive for many years. But the drugs are expensive and don't offer a cure. People with HIV also have a much higher risk of developing certain cancers, such as those of the lung, liver, head and neck.
Gallo is working with a team of researchers including institute colleagues George Lewis and Anthony DeVico. Tim Fouts, of Baltimore-based Profectus Biosciences Inc., a spinoff company from the institute, is also part of the team.
After Thursday's announcement, attended by Lt. Gov. Boyd Rutherford and University of Maryland School of Medicine Dean E. Albert Reece, Gallo said the vaccine holds much promise, but no guarantees quite yet.
"Can I promise absolute success? No," he said. "Do I hope it leads to a series of advances in the fields? Yes. And I think it will lead to some advances."
The road to FDA approval
The FDA requires a series of increasingly involved human trials before deciding to approve a vaccine for HIV.
Phase I: Tests the safety of a vaccine candidate in up to 100 volunteers for up to two years.
Phase II: Continues testing the safety of a drug candidate and whether it provokes an immune response in several hundred volunteers at risk of acquiring HIV.
Phase IIb: Tests the vaccine's effectiveness in a larger population of several thousand at-risk individuals. (The combined Phase II trials may last longer than two years.)
Phase III: Tests the vaccine's effectiveness in at least 10,000 at-risk individuals and monitors for adverse reactions for up to four years.
Source: National Institute of Allergy and Infectious Diseases