They discovered a promising weapon against measles

To develop new measles vaccines and treatments that stop this fusion process, researchers recently used an imaging technique called cryoelectron microscopy show in unprecedented detail how powerful antibody can neutralize virus until the merger process is completed.

“What’s interesting about this study is that we found pictures of the nuclear fusion process in action” explains Professor, LJI President and CEO Erica Ollmann Saphir, who led the study published in Science along with Matteo Porotto, professor of molecular viral pathogenesis (in pediatrics) at Columbia University. “The series of images is like a pop-up book in which we see snapshots of the entire development of the fusion protein, but then we see the antibody binding to it before it can complete the final step of the fusion process. We believe that other antibodies against other viruses will do the same thing, but Images like this have never been captured before.

“Adds the expert.

In fact, this work may be relevant for more than just measles, since the virus is just one member of the larger measles family. paramyxovirus, which also includes the deadly Nipah virus. Nipah is known to be less contagious but causes a much higher mortality rate than measles.

“What we learn about the fusion process could have medical implications for Nipah, parainfluenza viruses and Hendra virus. All these viruses have pandemic potential.“Says first author of the study and LJI postdoctoral fellow David Zyla.

Despite extensive vaccination efforts, the virus remains a serious health threat. Measles was responsible for about 136,000 deaths worldwide in 2022, with recent outbreaks in more than a dozen U.S. states, according to the World Health Organization and the U.S. Centers for Disease Control. The victims were mainly children under the age of five who were not or insufficiently vaccinated. .

“Measles Causes more childhood deaths than any other vaccine-preventable disease.and it is also one of the most contagious viruses known,” says Sapphire.

It’s not just young children who are at risk, Zaila said: “The current vaccine works well, but it should not be given to pregnant women or people with weakened immune systems.”

There is no specific treatment against measles, so researchers are looking for antibodies that could be used as an emergency treatment to prevent severe illness. To better understand how the measles virus fuses with cells, the LJI team turned to an antibody called mAb 77. The researchers found that mAb 77 targets the measles fusion glycoprotein, part of the viral machinery that measles uses to enter human cells through a specialized process. called a merger.

¿Can mAb 77 function as a therapeutic antibody? against measles? The researchers found that mAb 77 stopped the virus mid-fusion, when the fusion glycoprotein had already partially “folded” into the correct conformation for complete membrane fusion. Finally, the researchers were able to see exactly how mAb 77 joined the pieces of the fusion glycoprotein together to prevent viral infection. “It was amazing to see what that intermediate step in the fusion process actually looked like,” Zaila says.

Now that they know how mAb 77 works, the researchers are hopeful that the antibody can be used as part of a therapeutic cocktail to protect people from measles or to treat people with active measles infection.

In a subsequent experiment, the researchers demonstrated that mAb 77 provided significant protection against measles in cotton rat models of measles virus infection. Cotton rats pretreated with mAb 77 before exposure to the virus showed no infection or reduced signs of infection in lung tissue.

Looking to the future, Sapphire and Zayla are interested in studying different measles antibodies. “We’d like to stop the fusion at different points in the process and explore other therapeutic options,” Zayla says.

Zaila also plans to continue to work closely with measles researchers at Columbia University. “The combination of LJI’s expertise in structural biology and Columbia University’s expertise in cell biology and virology was key to moving this project forward,” he says.