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Naturally Occurring Antibodies Lead to a Potential HIV Vaccine

Naturally Occurring Antibodies Lead to a Potential HIV Vaccine

Scientists found existing antibodies capable of attacking a weakness in the virus. Now the trick is getting our immune systems to create more of them.

Scientists at The Scripps Research Institute (TSRI) published their findings in the November issue of Immunity, describing four prototype antibodies that can target one of HIV’s weak spots and use it to destroy the virus. Using what they learned from these antibodies, the researchers created a protein that mimics the molecular structure of an HIV protein to test a potential HIV vaccine.

“This study is an example of how we can learn from natural infection and translate that information into vaccine development,” said co-author Raiees Andrabi in a written statement. “This is an important advance in the field of antibody-based HIV vaccine development.”

These new findings build on recent studies showing that, the immune system can be prompted to develop specific antibodies and that those antibodies may be able to neutralize HIV.  (Other researchers have created artificial antibodies to target HIV).

 First, researchers engineered a molecule that mimics a vulnerability they had discovered on the virus then they introduce that molecule to the immune system, which creates antibodies in respond to the perceived threat. Then a second molecule was engineered and introduced, causing the immune system to production even more mature antibodies. This second engineered molecule has been previously shown to be an effective HIV vaccination in rabbits.

When those earlier results were released, the study’s senior author Dennis R. Burton (scientific director of the International AIDS Vaccine Initiative (IAVI) Neutralizing Antibody Center and of the National Institutes of Health  (NIH)’s Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVID) at Scripps. called their findings, “pretty spectacular."

"It worked much better than we expected," David Nemazee, another NIH researcher, told the San Diego Union-Tribune at the time.

In the new study, the Scripps researchers carried out a series of experiments involving virus modifications, protein and antibody engineering. They found that four antibodies targeted a single spot on HIV’s surface called the V2 apex. This was significant because the V2 apex could be recognized by these antibodies on about 90 percent of known HIV strains — and even related strains that infect other species (like SIV that attacks monkeys). This is essential to creating a vaccine capable of targeting all strains of HIV.

“This region helps stabilize the virus, so it’s an important area to target if you want to neutralize HIV,” said Andrabi.

Investigating further, the researchers noticed that two of the four antibodies had a particular feature that could prove especially important to the development of an HIV vaccine.

When a viral agent is identified, the immune system usually launches its initial attack by activating immune B cells that have a form of antibodies called “germline”, on the cell surface; which binds to invading pathogens. Just the first line infantry, germline antibodies arrive quickly but are rarely able to effectively knock out viruses alone. But as they become more and more familiar with the infective agent, the antibodies mutate and become better and better at attacking the invader. This creates what are called “developed” antibodies.

So researchers were quite surprised to discover that two of the four antibodies they were studying hadn’t yet mutated when they binded with the V2 apex. There was something about their basic germline structure that was able to fight HIV without having to mutate first.  

If humans naturally produce these antibodies that can attack HIV without having to develop into mutated variants, then why are so many people living with HIV? Unfortunately, the immune system seems to produce only a handful of these HIV-neutralizing germline antibodies. But the researchers believed they could encourage the immune system to produce more. To do so they just needed to find (and engineer copies of) proteins in HIV that the antibodies are particularly adept at recognizing and binding to.

In the new study, the researchers succeeded in mimicking a structure on HIV called the native HIV coat protein. The engineered proteins did indeed bind well to the germline antibodies, which should initiate a more effective immune response. The next step is to test an HIV vaccine based on these proteins (using the proteins to induce the creation of more productive antibodies, which could then attack HIV if exposed to the virus). The researchers hope to begin animal model testing soon.

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