Researchers used AI to identify an mpox protein that triggers a strong immune response in mouse models. The discovery could pave the way to more effective vaccines and therapies for mpox. The corresponding study was published in Science Translational Medicine.
"It would have taken years to find this target without AI. It was really exciting because no one had ever considered it before for vaccine or antibody development. It had never been shown to be a target of neutralizing antibodies,” co-lead author of the study, Jason McLellan, Professor at the Department of Molecular Biosciences at the University of Texas at Austin, said in a press release.
“Unlike a whole-virus vaccine that's big and complicated to produce, our innovation is just a single protein that's easy to make,” he added.
To begin, researchers identified 12 antibodies that neutralize the monkeypox virus after analyzing blood from people who either recently recovered from the virus or who had been vaccinated. They next used the AlphaFold 3 model to predict which of mpox’s viral surface proteins were likely to strongly bind to the patient-derived antibodies.
Ultimately, the model flagged a protein called OPG153 with high confidence. Lab tests confirmed that OPG153-targeting antibodies neutralized mpox clades Ib and IIb. The researchers also tested OPG153 in mice; those vaccinated displaying a strong neutralizing antibody response against mpox.
"We started with people who survived infection with monkeypox virus, isolated antibodies that they naturally produced and worked backward to find what part of the virus acted as the antigen for those antibodies. Then we engineered the antigen to elicit similar antibodies in mice," said McLellan.
The University of Texas at Austin has filed a patent application to use OPG153 and its derivatives as a vaccine antigen. As the monkeypox virus is closely related to the virus that causes smallpox, the findings may support the development of vaccines or treatment for smallpox as well.
Sources: Science Daily, Science Translational Medicine