World AIDS Day, Dec. 1, features the slogan “Getting to zero: zero new HIV infections, zero discrimination, zero AIDS related deaths” for the years 2011 through 2015.
While it is unlikely the “zero” goal will be reached by 2015, three decades of HIV analysis has sparked a “renaissance” of medical research that is leading scientists in new directions in their search for an effective vaccine.
Dr. Wayne Koff, the chief scientific officer for the International AIDS Vaccine Initiative, started researching HIV shortly after the first cases began appearing some 30 years ago.
“We’ve seen in the last three or four years a plethora of data that we in the AIDS vaccine development field are calling a renaissance, and as someone who has been in the field since the beginning I don’t use that term lightly,” Koff said.
It took almost 20 years of research to get AIDSVAX, the first potential vaccine, into human testing in 2003. While that vaccine didn’t reduce viral load, Koff said it was important because “it proved that we could safely conduct an HIV human efficacy trial.”
That trial eventually paved the way for the 2009 Merck RV144 trial in Thailand. That study included more than 16,000 participants studied over a course of six years.
“In a surprise to many of us in the field, this showed a modest efficacy of 31 percent when compared to control group,” Koff said. “While that wouldn’t result in a workable vaccine because the efficacy was only 31 percent, it did show that a vaccine was possible, and there have been several studies examining why that vaccine was effective.”
According to the International AIDS Vaccine Initiative there are at least 37 different vaccine trails currently underway across the globe, each exploring different potential cures, and each providing key information in the search for an effective vaccine.
Koff said that in order to make a product that could be given to the public, a vaccine would have to be at least 50 percent effective in testing. For example, the Centers for Disease Control & Prevention estimates that the yearly flu vaccines have efficacy rates of around 50 to 70 percent.
‘Different virus in each person’
Finding a vaccine for HIV has proven so difficult in part because of the nature of the virus. Because of its ability to change, HIV has required a new approach.
“Because this virus mutates so much we can’t just use the old form of using a weakened form of the virus,” Koff said. “The measles vaccine that’s licensed is just a weakened form of measles. The licensed polio vaccine is a weakened version of polio, but HIV is a crafty virus… and we learned a long time ago that you can’t just take a weakened version of HIV.”
Viruses are non-living pieces of proteins wrapped around either DNA or RNA. Viruses cannot reproduce on their own, and so they invade cells and take over the cell’s machinery to make copies of themselves, which often destroys the cell in the process. Because HIV is an RNA virus it has been especially difficult to treat.
“It is an RNA virus which is prone to making mistakes, unlike DNA. If it makes too many mistakes then it stops being HIV, but if it makes a standard amount of mistakes that RNA replication typically makes, it changes the amino acids, and makes a different virus,” Koff said. “HIV is different across the world, and the isolates are very different in each individual. It’s essentially a different virus in each person.”
Because of that, researchers have different ways to stop the virus, and many of the vaccine candidates target the protein capsule that carries the DNA. Koff said researchers are finding more sites on HIV that are unique to that virus and can be blocked by broadly neutralizing antibodies.
Think of a lock and a key, Koff said. If you have a molecule of a T-Cell, that part is only going to go into a receptor on HIV. If researches can bind that site and keep that virus from infecting the cell, the spread of HIV in the body can effectively be stopped, Koff explained.
Human trials under way
Another factor that makes the virus more deadly is that it infects T-Cells, a type of white blood cell that is a critical link in the body’s immune system. Attacking the T-Cells and using them as a host helps allow the virus to spread, and leaves the body open to secondary infections.
A former Emory University researcher, Dr. Hariett Robinson has been exploring a multi-stage attack that she thinks could result in a vaccine that could not only keep people from being infected, but reduce the viral load in people who are already HIV positive.
Robinson has worked on the vaccine for over a decade and has moved to GeoVax, a private company dedicated to making a vaccine, where she serves as chief scientific officer.
Her vaccine consists of DNA modified to prime an immune response and an inert virus that could boost an immune response.
“The DNA prime is sort of like pouring water down a pump, where you pour a little bit of the pump down the well to prime it. It’s the little bit that allows your body to recognize the virus and fight it,” Robinson said.
Robinson’s vaccine started Phase II human trials in January 2009 and involves 225 participants at sites in the United States, including Emory University’s Hope Clinic, and South America.
The next stage, scheduled to start in 2014 and last three years, would examine high risk populations, which would include gay men.
Robinson’s team is also moving forward with a separate trial to test if the vaccine can control the infection in those who have already been exposed.
“For people who are positive already, we have a therapeutic application that we are working on, and we have a very small open label trial going on,” Robinson said. “In that trial we have several people who have recently undergone seroconversion. They go on drugs within 18 months of their infections, and they have to have the virus well controlled and then we give them the vaccine.”
‘Crafty virus’ still kills millions
HIV research has seen unparalleled expansion in the years since Merck made the results of the Thailand trial public.
“What we expect to see now, between now and the end of the decade, [is] a series of human efficacy trials that are building on the [Thailand] stories, that are building on the better vectors that have advanced into clinical trials,” Koff said.
Researchers routinely build on each other’s results and failures. Robinson’s vaccine is different from other previous vaccines because it includes a macrophage colony stimulating factor, which helps activate the immune system.
“They’re the ones that will see the virus-like particles and take that to the B-Cells and the T-cells to initiate the immune response,” Robinson said.
That vaccine uses techniques that have not been tested before, and more new studies are published nearly monthly.
In October, the Centre for the AIDS Programme of Research in South Africa reported finding two new vulnerabilities in the HIV protein coat. In November a Canadian research team announced successfully clearing Phase I human testing with a virus that uses dead HIV virus.
“There have been a series of vectors of vaccine candidates, some are weakened forms of viruses, some of them are different forms of boosts, some unique collections of antibodies… there are a number of studies that are about to go into trials that — just based upon the results in the primate studies — look to have a better chance at being more effective then the studies that have come before them,” Koff said.
While there are more studies using newly discovered techniques in the hopes of finding an effective cure, researchers are leery of setting timelines, or making overly optimistic predictions.
Even if Robinson’s vaccine proves to be highly effective it would be years before it is available to the public.
“For the preventive vaccine? I really think we’re going to have it, but I think it’s going to take at least five years, and then it’s going to be years before we can a make a product that we can manufacture that your doctor can give you,” Robinson said.
Koff is often asked if HIV could ever be fully eradicated like small pox and said he doesn’t know the answer.
“I don’t know if we know enough to fully answer that,” he said. “The reality is that we need a vaccine first. We have a lot of other tools in the tool box about HIV prevention, but without a vaccine it’s unlikely that we’re really going to be able to end the epidemic.
“I want to emphasis that, because every day you hear stories about … education, condom use, circumcision,” Koff added. “But even with all of those we still have over 7,000 HIV infections every day, and several million deaths from AIDS every year. The virus is crafty enough that it continues to find ways above and beyond our current prevention methods.”
Top photo: World AIDS Day, Dec. 1, features the slogan ‘Getting to zero: zero new HIV infections, zero discrimination, zero AIDS related deaths.’