Developing a new path to an HIV vaccine

(From left to right) Professor of virology Qingsheng Li and professors of chemistry, Wei Niu and Jiantao Guo, are working on a new method that could result in a safe, HIV vaccine. (Photo courtesy Troy Fedderson, University Communications)
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July 1, 2014 - 6:30am

Scientists fighting AIDS have changed the disease from a death sentence to a livable condition thanks to treatments and medicines developed over the past 30 years. But so far, no one has been able to develop an effective vaccine against HIV, the virus that causes AIDS. NET News looks at how researchers from the University of Nebraska-Lincoln are trying to develop a new path towards an HIV vaccine.


First, let’s review what a vaccine is. It isn’t a cure. Vaccines teach your immune system to recognize and fight off a disease.

“They generate some memory protective immune response so they can recognize the pathogen or viruses in here. And they kill the virus during the initial invasion,” Qingsheng Li, professor of Virology at the University of Nebraska-Lincoln, said.

UNL researchers modified the HIV genome so that it needs an amino acid it doesn't normally need to produce the protein it needs to replicate and infect cells. (Figure courtesy Jiantao Guo, University of Nebraska-Lincoln)

For instance, when you get injected with the chicken pox vaccine, your immune system reacts to it like a real virus. Then, when you’re exposed to the regular chicken pox, your immune system already has the tools called immunogens to fight against it.

The chicken pox vaccine contains a live, but weakened version of the actual virus in it. Other vaccines, like polio, contain a dead version of virus. Live virus vaccines are generally more effective because they generate a stronger reaction from your immune system, and results in longer lasting immunity.

But it’s tricky to develop a vaccine for HIV.

“With many live virus vaccines people can get actual disease from the vaccine. And so for some diseases, where you get a mild case of mumps or something, that’s really not so terrible. But if people get infected with HIV from the vaccine, that’s a big deal,” Susan Swindells, professor of medicine and director of the HIV clinic at the University of Nebraska Medical Center in Omaha, said. This is a risk with any kind of live virus vaccine. With HIV, it’s riskier only because HIV itself is more dangerous. As Swindells said, “It doesn’t go away.”

To make a live virus vaccine for HIV, researchers have to stop the virus from being able to infect cells. But it’s hard to change how HIV behaves. HIV replicates incredibly quickly which means it can respond rapidly to anything that makes it harder for it to infect cells. To make it more complicated, there are a lot of different strains of HIV all over the world, and there can be multiple strains of HIV found in a single person, depending on what treatments they’ve received.

How does HIV work?

A virus, at its simplest, is a strain of RNA or DNA that copies itself over and over again.HIV, like all viruses, replicates by altering its hosts' cells to create more copies of itself. Here's how a virus infects:

  • A virus inserts a bit of its genome into a host cells' DNA.
  • That cell begins to produce copies of virus instead of what it normally does.
  • Eventually, the cell will fill up with copies of virus and burst, spreading viruses further throughout your body.
  • These new viruses repeat the process on more of its hosts' cells.

HIV is special in a couple ways.

  • It's very effective at infecting white blood cells – the main defenders in your immune system. Once white blood cells are infected, they no longer recognize HIV as a threat, making it even easier for HIV to infect more cells.
  • HIV is also a retrovirus. Its genetic material is in RNA,but its host organisms have DNA. HIV is able to insert its RNA into a host cell's DNA and then have that cell produce RNA instead of DNA.

“HIV is just a challenge. People used all the conventional way to try to make vaccine, it doesn’t work. So you have to think outside the normal approach,” Li said.

New research

Li is one of three researchers at UNL working on a method to weaken  HIV  so it can be used safely in a live virus vaccine. Li workd with chemistry professors Jiantao Guo and Wei Niu. According to Niu, she and her colleagues are trying something new to weaken HIV.

“Basically we use synthetic biology approach to control the virus replication,” Niu said.

That means that Niu and her fellow researchers are going in and changing the virus’s genetic material – its genome. In humans, that’s what’s encoded in your DNA. Viruses, like HIV, have something similar called RNA.

Niu, Guo, and Li changed HIV’s genome so that it needs what they call an unnatural amino acid ¬– one the virus doesn’t normally need and isn’t found in humans – to make the proteins it needs to replicate and infect its host. Niu remembers when they started trying to find a way to modify HIV’s genome.

“So, at the beginning, we generate a couple of mutants.Like mute-1, mute-2, of the HIV virus. However, they didn’t really work. Eventually we have to generate mute-3, 4, 5, 6, 7, 9. 10. Totally 10 different mutants,” Niu said.

It wasn’t until the second Christmas that they finally saw their research working: their virus couldn’t replicate without the extra amino acid.

This is a big first step in developing a vaccine. Remember how HIV is able to respond to anything stopping it from infecting cells by replicating really quickly? That’s one of the big risks in making a live virus vaccine for HIV. Niu, Guo, and Li are trying to build a switch to stop HIV from replicating period so that it can’t adapt and become infectious again. According to Li, this research could make it safer to use live viruses in vaccines in general.

“So this kind of engineering, potentially, we can dramatically reduce the risk,” Li said.

Why does a vaccine matter?

Building an effective HIV vaccine would be huge. While HIV IS treatable today, it’s also still a problem. HIV hasn’t stopped spreading. Nebraska has seen roughly 60-90 new diagnoses of HIV every year for the past decade. Swindells estimates about 20 percent of HIV-positive people in the United States don’t know they have HIV.

“There’s a lot of people who are not on treatment, not in care, or unaware of their diagnosis that still fuel the spread of new cases. So we haven’t made any impact in the number of new cases every year for several years now. It’s about 50,000 new patients every year in the US,” Swindells said.

This is still a really early part of vaccine development. This research so far has already taken two years. Niu, Guo, and Li just got a major four-year grant from the National Institute of Health and the National Institute of Allergy and Infectious Diseases, which they’ll use to move from testing the modified virus on cells to animals. It could be at least 15 years before a vaccine comes out of this research. Most vaccines turn out to be ineffective before even reaching human trials. There are a lot of obstacles left.

HIV in Nebraska

New HIV diagnoses in 2012: 83

New HIV diagnoses in 2009: 69

New HIV diagnoses in 2006: 75

Data courtesy Nebraska Dept. of Health and Human Services

Li says that’s partly why he enjoys this research so much.

“I think it’s a challenge, but fun. It’s always a challenge because science always in essence is new, novelty. And we generally feel very excited by the new and the unknown,” Li said.

Right now, there aren’t any HIV vaccines on the market. According to the International HIV Vaccine Initiative database, there are 35 clinical trials for an HIV vaccine currently ongoing in the whole world. Most of them are in the first stage of clinical testing on humans.

Discussion

 

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