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Lucy Chard
27 Oct 2022

Lassa virus antibody cocktail could be the first step in developing a vaccine

Cover of Science Translational Medicine, Credit: Niámh Mundy, Phospho Biomedical Animation.

A research team from La Jolla Institute for Immunology in California, USA, have identifed a trio of antibodies that could be used to neutralize the Lassa virus

Researchers from La Jolla Institute for Immunology (LJI; CA, USA) have shown how a concoction of antibodies could be used to develop a vaccine for Lassa virus.

Lassa virus, a virus endemic to West Africa, gives rise to Lassa fever, which causes flu-like symptoms and affects around 300,000 people each year. The fever can lead to more severe symptoms and be fatal; pregnant women are particularly vulnerable with 90% of infections leading to death.

The Lassa virus has been under investigation by the Saphire lab at LJI for several years, studying images of the Lassa virus glycoprotein so that they can identify weaknesses – epitopes – that could be taken advantage of in finding a treatment option.

Recently, the researchers were able to isolate three rare antibodies from the blood of survivors of Lassa virus infection, with the hope that therapeutics based on these antibodies could be developed.

Initially, it was thought that antibodies would not be effective in protecting against Lassa virus, but by studying the structural map of the Lassa virus glycoprotein and using a combination of the three neutralising antibodies, the team were able to develop a ‘cocktail’ for testing.

This cocktail – named Arevirumab-3 – was tested in non-human primates, including those with an advanced form of the infection, and was proved to be 100% effective in treating the disease.

The next step was to test the cocktail in humans, where the team ran into a roadblock as the US FDA requires the mechanism of action to be clear before approving the launch of clinical trials.

The team were able to produce a glycoprotein that was an exact copy of the natural protein found on the Lassa virus, and this could be recognised by the three antibodies that made up the cocktail of Arevirumab-3. They then used cryo-electron microscopy single-particle analysis to produce high-resolution structural images of all of the elements, along with functional assays to show exactly how each of the antibodies bind to the glycoprotein.

“Lassa has another trick. It shields itself using a thick coat of human carbohydrate molecules—like a wolf in sheep’s clothing,” explained Erica Ollmann Saphire, lead researcher from LJI, “Haoyang’s [Haoyang Li, Instructor in the Saphire Lab, LJI] structures clearly show how these potent, protective antibodies breach or even utilize the carbohydrates to target and neutralise the virus.”

The stages of research have been published throughout the past year.

Saphire stated: “This body of work now offers the first-ever full-epitope map, revealing every vulnerable target of the Lassa glycoprotein.”

From this, the team will be able to move Arevirumab-3 into clinical trial phases and hopefully develop a vaccine to protect against Lassa virus in the near future.

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