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Potent Antibodies Offer New AIDS Vaccine Design

  • Joe DeCapua

Researchers say powerful antibodies may hold clues to developing an effective AIDS vaccine. The antibodies were isolated from individuals already infected with HIV.

Dr. Wayne Koff says the goal is to find a vaccine that will help the immune system fend off an HIV infection.

“Most vaccines work in terms of stimulating something known as antibody, which is a protein substance in the body. And they work because the antibody identifies the site on the virus. And it can attach onto the virus and kill it,” he said.

Koff, chief scientific officer for IAVI, the International AIDS Vaccine Initiative, said the problem with HIV is that it’s a hyper-variable virus.

That means it’s different all over the world. And so instead of a single strain or a couple of strains, we have millions of strains. And as a result, for a vaccine, instead of eliciting a neutralizing antibody, what one is attempting to do is to identify where the vulnerable sites on the virus that are the same on every virus particle. And these antibodies then are known as broadly neutralizing antibodies. So if you’re exposed to a virus on one side of the globe, they would work just as well as if you’re exposed in some other region of the world.

HIV becomes hyper-variable when it replicates. Each time, it’s just a little bit different. Some scientists call these changes minor errors, but it’s enough to confound the human immune system. The changes occur in the outer protein of the virus, the target of neutralizing antibodies. In other words, the weak spot.

Only a few have them

The 17 antibodies that were isolated came from people infected with HIV.

Koff said, “We screened about 1,800 people. About one percent of the individuals had extremely broad and potent neutralizing antibodies against HIV. We then went back to these individuals and we took additional samples of blood and from those individuals we identified these broadly neutralizing antibodies.”

Did the people who produced these antibodies do better at fighting HIV? No, they didn’t.

“Most people would think if one has broadly neutralizing antibodies after HIV infection there should be a benefit. And that is not the case. In the case of individuals that are already HIV infected, the virus is always one step in front of the immune system,” he said.

But the immune system could react differently if it had these antibodies before infection.

“The real challenge for us and from a vaccine point of view is to ensure that the immune system is primed in advance of the virus as opposed to after HIV infection. It remains to be seen if these antibodies will have any therapeutic benefit,” he said.

Now what?

The next step is animal studies. The antibodies will be given to chimpanzees to see whether they can block an HIV-like virus. Koff says initial vaccine candidates will probably be ready in three or four years.

The antibody research is outlined in an article in Nature magazine. It was funded by IAVI, The Scripps Research Institute, Theraclone Sciences and Monogram Biosciences, Incorporated.

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