A new study highlights an innovative approach to measles prevention and treatment, focusing on non-live virus vaccines and targeting viral proteins to safeguard immunocompromised populations and tackle measles complications more effectively.
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Mechanism of antibodies binding to a measles fusion protein assembly and stopping it from fusing with the cell membrane. Credit: Digizyme for Columbia University Irving Medical Center
Innovating Measles Prevention
Porotto’s group has been working to develop a new measles vaccine that does not rely on live virus and can be used to protect immunocompromised people.
The current vaccine, which contains an inactivated or weakened form of the measles virus, mainly generates antibodies against hemagglutinin, a protein that helps viruses attach to cells.
Porotto’s team is trying a different approach: isolating specific components, or subunits, of the virus to generate antibodies towards other important proteins. Since subunit vaccines do not contain the whole virus, they are safer for people with weakened immune systems.
The component the researchers targeted was the fusion protein, which helps the virus enter the cell and cause infection. They found that antibodies targeted towards the fusion protein successfully prevented the virus from completing its merger with the cell membrane.
Advances in Measles Treatment
At the same time, Porotto’s team had been looking for ways to treat measles encephalitis, an often-fatal complication in which the infection spreads to the brain.
They found that mutant forms of the measles virus found in the brains of people with measles encephalitis contain modified fusion proteins.
When the researchers investigated this variant of the fusion protein with cryo-electron microscopy (cryo-EM), they obtained a frozen snapshot of the action at each step, giving them critical insight into how the antibody they created interacts with the virus.
“We discovered that our antibody binds the pre-fusion state of the protein, but it doesn’t completely prevent the protein from working,” says Porotto.
Even after the antibody latched onto the protein, the protein was able to transform itself into an intermediate state, initiating the fusion of the virus and cell membrane. But the antibody prevented the fusion protein from completing this process, essentially blocking infection.
Porotto and his team say that the intermediate-state stabilization makes the antibody highly effective.
Looking Forward in Measles Research
The team is now in the process of testing the efficacy and safety of a novel set of stabilized measles fusion proteins as a subunit vaccine for immunocompromised individuals and for vaccinated individuals with waning immunity.
For more on this study, see Stopping Measles With Groundbreaking Insights From Cryo-EM.
Reference: “A neutralizing antibody prevents postfusion transition of measles virus fusion protein” by Dawid S. Zyla, Roberta Della Marca, Gele Niemeyer, Gillian Zipursky, Kyle Stearns, Cameron Leedale, Elizabeth B. Sobolik, Heather M. Callaway, Chitra Hariharan, Weiwei Peng, Diptiben Parekh, Tara C. Marcink, Ruben Diaz Avalos, Branka Horvat, Cyrille Mathieu, Joost Snijder, Alexander L. Greninger, Kathryn M. Hastie, Stefan Niewiesk, Anne Moscona, Matteo Porotto and Erica Ollmann Saphire, 28 June 2024, Science.
DOI: 10.1126/science.adm8693
All authors: David Zyla (La Jolla Institute for Immunology); Roberta Della Marca (Columbia University); Gele Niemeyer (La Jolla Institute); Gillian Zipursky (Columbia University); Kyle Stearns (Columbia University); Cameron Leedale (Ohio State University); Elizabeth Sobolik (
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