Shape-Shifting Molecule Suppresses HIV

Teresa Feng

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Last November, Scripps Research discovered the HIV envelope protein Env, which could prove to be a promising candidate for an HIV cure. This shape-shifting molecule has access to the immune system of the infected patient, and it plays a major role in preventing the spread of the infection. Env has proven to be effective on various HIV strains in mice and rabbits by releasing an antibody that prevents the spread of HIV. Jiang Zhu, an associate professor at Scripps College, sees the usage of Env to find an applicable vaccine as a significant advancement in the research of HIV. However, because Env is such a complex molecule, scientists struggle to keep it in its stabilized “closed” shape when entering an infected subject’s bloodstream.

HIV infects CD4 cells by fusing with the cell, taking control of the DNA, and then replicating itself to release more of the HIV virus into the blood. When stabilized, the Env proteins release the antibody and stop the virus from replicating and spreading through the bloodstream.

According to Science Daily, “The idea has been to inoculate people with the whole Env protein or subunits of it to stimulate the production of Env-binding antibodies, in the hope that these antibodies will preven HIV from infecting host cells in future exposures to the virus.” If HIV does not infect the cell, there will be no virus.

Though researchers have had difficulty controlling Env’s shape-shifting, they may have discovered a method to stabilize the molecule and maintain the desired shape. Env molecules gather in groups of three called trimers and radically change in shape before and after infecting cells. To serve as a useful vaccine, Env has to be delivered in either its pre-infection state or the shape it has when it is in the immune system and first on an HIV virus. When researchers attempted to use the non-optimal Env protein state, infection was only prevented among a few HIV strains, which meant it was not suitable as a general solution. According to Precision Vaccinations, Jiang Zhu and his colleagues at Scripps Research reported that “Modifying a short, springy section of Env called HR1 might do the trick— it allowed Env to stay in the pre-infection, ‘closed’ shape.” They modified the HR1 from thirty to forty strains of HIV, and it was successful in preventing the infection. Experimentation has been very effective on mice and rabbits, and researchers intend to use this strategy on monkeys as well.

Ufovax LLC is now sponsoring research at Scripps, which includes testing different vaccines that are based on Env trimers or, more specifically, the HR1. Researchers are also planning and testing a new vaccine that is a combination of all three tested potential vaccines. This breakthrough is expected to open up new opportunities after thirty years of HIV research and ultimately result in a successful product that will serve as generalizable vaccine for HIV.