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Antibody That Penetrates HIV's Weak Spot Could Lead to Future Vaccine


 

In the movie “Independence Day,” remember how everyone was trying to figure out how to penetrate the mother ship’s defense shield and find just the right spot to get inside the star craft and blow it into bits?

Finding a way to stop HIV is kind of like that. In the quest for a vaccine, finding broadly neutralizing antibodies that will work on a variety of strains – a weak spot in HIV’s outer envelope – has proven incredibly difficult.

Now scientists at The Scripps Research Institute have discovered four prototype antibodies that target a specific weak spot on the virus. The antibodies come from HIV-positive donors. They appear early in infection, are potent, cross-reactive and do not generally display autoreactivity, meaning they don’t elicit a dangerous autoimmune response.

Their description of the antibodies in the research published this week in the journal Immunity reads like science porn. "An important characteristic of this group of antibodies is their extraordinarily long CDHR3 loop (>24 amino acids), which helps them to penetrate the glycan shield on the Env spike trimer and access the protein surface below.”

Translated: They get the job done when it comes to attacking HIV. They target a spot on HIV’s surface called the V2 apex. “This region helps stabilize the virus, so it’s important to target if you want to neutralize HIV,” said Scripps research associate Raiees Andrabi in a Scripps news release. “This study is an example of how we can learn from natural infection and translate that information into vaccine development. This is an important advance in the field of antibody-based HIV vaccine development.”

The findings build on previous TSRI studies that show how the immune system can develop antibodies that neutralize many strains of HIV when prompted.

“In the new study, the researchers carried out a series of experiments involving virus modifications, protein and antibody engineering,” according to the news release. “Investigating further, the researchers noticed that two of the four antibodies had an unusual feature that could prove important in vaccine design.”

While the immune system generally fights infection by expressing antibodies that cannot at first bind to a virus but can do so after mutating, these two antibodies “did not need to mutate to bind with the V2 apex,” the news release reports. “Instead, these antibodies used part of their basic germline structure, encoded by non-mutated genes.”

The problem is the immune system does not produce enough of these antibodies. “In the new study, the researchers succeeded in mimicking a structure on HIV called the native HIV coat protein,” the news release explains. “This let them design proteins that do indeed bind well to the germline antibodies and hopefully start a useful immune response. The next step will be to test the vaccine candidates in animal models.”