Breakthrough in Measles Research: New Antibody mAb 77 Shows Promise

Measles News: When the measles virus encounters a human cell, it initiates a complex process that allows it to merge with the host cell membrane. This process is called fusion, and once it is complete, the virus takes over the host cell entirely, allowing it to replicate and spread. This makes the measles virus incredibly efficient and dangerous, especially in populations where vaccination rates are low.


Breakthrough in Measles Research: New Antibody mAb 77 Shows Promise
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Scientists at the La Jolla Institute for Immunology (LJI) Center for Vaccine Innovation have been diligently working on new ways to stop this fusion process. Their goal is to develop effective vaccines and treatments against measles. By preventing the virus from completing its fusion process, they aim to stop it from spreading and causing severe disease.
 
A Closer Look at Viral Fusion
To gain a deeper understanding of how the measles virus operates, the LJI team used an advanced imaging technique called cryo-electron microscopy. This technique allowed them to capture detailed images showing how a powerful antibody can neutralize the measles virus before it completes its fusion process. The study, led by Dr Erica Ollmann Saphire, Ph.D., and Dr Matteo Porotto, Ph.D., provides unprecedented insights into the virus's behavior and potential ways to stop it.
 
Dr Saphire told media and Measles News outlets, "The series of images is like a flip book where we see snapshots along the way of the fusion protein unfolding, but then we see the antibody locking it together before it can complete the last stage in the fusion process.”
 
 This discovery is not only significant for measles but also for other viruses within the paramyxovirus family, such as the deadly Nipah virus, which shares similar fusion mechanisms.
 
The Ongoing Threat of Measles
Despite extensive vaccination efforts, measles remains a significant health threat, particularly for children. The World Health Organization and the U.S. Centers for Disease Control reported that measles caused around 136,000 deaths globally in 2022. Many of these deaths occurred during outbreaks in the United States, primarily among unvaccinated children under five.
 
"Measles causes more childhood deaths than any other vaccine-preventable disease, and it's also one of the most infectious viruses known," explains Dr Saphire. The current measles vaccine is highly effective, but it is not suitable for everyone, such as pregnant individuals or those with compromised immune systems. This limitation underscores the urgent need for new treatments.
 
The Role of Antibody mAb 77
To better understand how the measles virus fuses with human cells, the LJI team focused on an antibody called mAb 77. This antibody targets the measles fu sion glycoprotein, a crucial component that the virus uses to enter human cells. By binding to this glycoprotein, mAb 77 can potentially prevent the virus from completing its fusion process.
 
The researchers aimed to determine if mAb 77 could serve as an effective therapeutic antibody against measles. They engineered a version of the measles fusion glycoprotein that was stable enough to be imaged with cryo-electron microscopy. This engineering feat involved collaboration with scientists at Columbia University, who had previously identified stabilizing mutations in a measles variant that attacks the central nervous system.
 
Engineering the Fusion Glycoprotein
Creating a stable version of the measles fusion glycoprotein was a significant challenge. Dr Porotto's team at Columbia University had identified mutations in a measles variant that allowed it to invade the central nervous system. These mutations weakened the virus's structure, but the virus compensated by evolving additional stabilizing mutations.
 
Using this information, the study team engineered a version of the fusion glycoprotein that included these stabilizing mutations. This version was stable enough to be imaged with cryo-electron microscopy, allowing the researchers to capture detailed images of the fusion process.
 
"We got extremely good yields for the glycoprotein, which also enabled us to do structural biology and biochemical and biophysical studies," the study team commented. This success allowed the team to capture clear images showing how mAb 77 interferes with the fusion process.
 
Membrane Fusion, Interrupted
The cryo-electron microscopy images revealed that mAb 77 binds to the fusion glycoprotein during the fusion process, locking it in an intermediate state and preventing it from completing the membrane fusion necessary for infection. "It was striking to see what this intermediate step in the fusion process actually looks like," the study team said.
 
By locking the glycoprotein in this intermediate state, mAb 77 effectively stops the virus from entering human cells. This discovery provides valuable insights into how the measles virus operates and offers a potential new avenue for treatment.
 
Potential for New Treatments
Armed with this new understanding of how mAb 77 works, the researchers believe it could be part of a treatment cocktail to protect against measles or to treat active infections. In experiments using cotton rat models, mAb 77 provided significant protection against measles, reducing infection signs in lung tissue.
 
"We'd like to stop fusion at different points in the process and investigate other therapeutic opportunities," the researchers said. Further collaboration with measles researchers at Columbia University will continue to drive this research forward.
 
The combination of expertise from LJI and Columbia University has been crucial in advancing this project. The combination of structural biology expertise from LJI and cell biology and virology expertise from Columbia was key to pushing this project forward.
 
Broader Implications for Viral Research
This groundbreaking study has opened new avenues for developing treatments not only for measles but also for other viruses with similar fusion mechanisms. The detailed insights into the fusion process provided by this research could help scientists develop targeted therapies for other paramyxoviruses, such as the Nipah virus, which is known for its high mortality rate.
"What we learn about the fusion process can be medically relevant for Nipah, parainfluenza viruses, and Hendra virus," said the study team. These viruses have the potential to cause pandemics, making it crucial to understand how they operate and how they can be stopped.
 
Conclusion
The discovery of how the antibody mAb 77 interferes with the measles virus fusion process marks a significant milestone in viral research. By understanding the detailed mechanisms of this process, researchers can develop targeted therapies to prevent and treat measles, offering hope for a future with fewer outbreaks and improved health outcomes for vulnerable populations.
 
This research highlights the importance of continued collaboration and innovation in the fight against infectious diseases. As scientists uncover more about the fusion mechanisms of viruses, they pave the way for new treatments that could save countless lives.
 
The study findings were published in the peer reviewed journal: Science.
https://www.science.org/doi/10.1126/science.adm8693
 
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