What's holding us back from having an HIV vaccine?

SmartPlanet takes a look at current roadblocks to an HIV vaccine, and our best hopes for innoculating against the virus in the future.
Written by Audrey Quinn, Contributor

This week on the site BBC Future, science journalist Ed Yong posted a thoughtful in-depth examination of the search for an HIV vaccine.

He begins his article with one of history's major healthcare disappointments:

On 23 April 1984, Margaret Heckler, the US Secretary of Health and Human Services, told the world that scientists had identified the virus that was the probable cause of AIDS. She was correct. She also said that a vaccine would be “ready for testing in approximately two years.” She was wrong.

Let’s back up a minute. Vaccines expose a person’s immune system to a small part of a disease causing agent. In doing so, the vaccine "teaches" the immune system to recognize and defend against that disease causing agent when a person encounters it in the outside world.

In the case of HIV vaccine, clinicians hope to teach the immune system to recognize HIV through injections containing a few genes of HIV. I talked with Dr. Karen Mark, clinic co-director of Seattle's HIV Vaccine Trials Unit.

"The HIV virus and all human things are made up of genes," Mark explains, "but there are many different genes that make up the entire virus, so what we do is take just little teeny bits of that genome or specific genes, that are made in the lab, and use this to make a vaccine."

Having little pieces of the HIV genome injected into you -- isn’t that a little risky? Dr. Mark works vigilantly to correct this misconception.

"We don’t have the whole genome," she says, "so it’s impossible for little bits of genes to somehow recombine and make HIV, if that makes sense. It’s like, if you have a head and an arm and a leg of a person, that’s not going to recombine somehow and make an entire person."

If such a vaccine would be safe, why do we still not have one? Here are some of the major setbacks:

1) HIV is one ninja of a virus

As Yong points out, HIV turned out to be the most diverse virus science has ever known.

It mutates so rapidly that people might carry millions of different versions of it, just months after becoming infected...So, creating an HIV vaccine is like trying to fire a gun at millions of shielded, moving targets. Oh, and they can eat your bullets.

Ideally the HIV vaccine would train your immune cells to target gp120, the surface protein that the virus uses to attach itself to your cells. But it is constantly mutating. If your cells were trained to attack gp120 at one moment, they wouldn't recognize its shape the next. The surface protein also protects itself by grouping in clusters of three covered by bulky sugar molecules, making it difficult for your immune system to find.

2) We can't watch how people recover from HIV naturally -- because they don't.

Researchers seeking cures often look to examples of how some people recover naturally from a microbe. Yong reports that doctors have not seen a single documented case where someone completely eliminated the virus from their body.

3) Past vaccine attempts have brought highly publicized failures.

Three have made it through clinical trials. Here's Yong's account of the first two:

Vaxgen’s AIDSVAX vaccine, consisting of two fragments of the gp120, failed to provide any protection. Merck’s v520 vaccine, consisting of a harmless cold virus carrying three HIV genes, fared even worse. It was meant to marshall immune cells called T-cells to kill off infected cells. It failed. Worse still, the trial had to be stopped early because vaccinated people seemed to be more susceptible to infections, for reasons we still do not fully understand.

I talked with Seattle's HIV Vaccine Trials Unit’s outreach coordinator David Garcia about the Merck v520 vaccine failure.

"In that particular trial there was a subset of individuals that, it could have been that the vaccine may have made them more susceptible to HIV, but those individuals were also people who had higher antibodies to the vector of the vaccine, and they were also uncircumcised."

Garcia points out that it is likely that other variables (besides the vaccination) may have predisposed those individuals to higher HIV infection rates.

The third trial, with 16,000 people in Thailand in 2009, held a sliver of hope. The vaccine on trial was a combination of two vaccines, which had failed individually, but when combined together proved to lower one's risk of infection by 31%. Promising, but 31% reduced risk makes you no where near immune to the virus.

Yong does, however, have hope for future HIV vaccines. He writes:

It turns out that many HIV patients carry secret weapons – “broadly neutralising antibodies” – that can attack a wide range of HIV viruses. For these patients, it is too late. Their infections are already in full swing and the virus can mutate around their defences. But the discovery proved that HIV’s vaunted diversity is not the roadblock for vaccines that many scientists feared. If we taught the immune system to make these antibodies early, we could destroy the virus before it gained a foothold.

Scientists are beginning to pinpoint the parts of HIV’s surface proteins that stay the same while the rest mutate. And more importantly, they're beginning to find antibodies that specifically target these conserved regions. Clinical trials of vaccines aimed at those antibodies are set to start in early 2013.

And while researchers continue to fine tune an HIV vaccine, the rest of us can work towards perfecting the HIV-fighting tool we already have, education.

Photo: UK Department for International Development/Flickr

This post was originally published on Smartplanet.com

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