Measles-Flu Comparison Yields Insights for Vaccine Design
By comparing flu viruses to the virus that causes measles, researchers fine-tuned a tool that may enable faster vaccine design.
By comparing flu viruses to the virus that causes measles, researchers fine-tuned a tool that may enable faster vaccine design, according to a study led by Mount Sinai researchers and published online this week in the journal Cell Reports.
The study results revolve around viruses, which are designed perfectly by evolution to invade human cells, inject viral genes and use human genetic machinery to make copies of them. In an endless back and forth, human immune cells have evolved to recognize and attack viral surface proteins, and viruses to constantly change their surface proteins to avoid being recognized. Called antigenic drift, these viral genetic changes proceed at different speeds in different viruses, with implications for vaccine design. While one childhood vaccination provides lifetime protection against measles, for instance, people need a different flu shot every year. The field has long known that flu viruses are much “tolerant” of constant change in certain genes than measles, but not why.
The answer may advance the design of vaccines that target parts of flu viruses they cannot afford to change, the so-called “universal” flu vaccines that would provide permanent immunity. Beyond flu, the new study validates a method that may help the field more quickly design vaccines that provide permanent protection when new and deadly viruses emerge.
“Our team used the measles virus to test a tool that offers a new way to measure the resistance of key viral genes, and related proteins, to change,” said lead study author Nicholas Heaton, PhD, a post-doctoral fellow in the Department of Microbiology at the Icahn School of Medicine at Mount Sinai. “It’s vital to quickly determine the parts of a virus so vital to its survival that it can’t randomly change them because they often make the best vaccine components.”
The field has long understood that key parts of the gene code for the measles virus remain unchanged over time, while similar genes in flu viruses constantly change, despite the two both being RNA viruses that infect the lungs. Specifically, the new study found that measles is much less able than the flu to survive genetic changes to the viral surface protein hemagglutinin or H. This protein is central to this story because it both enables viruses to latch onto cells and is well known to human immune cells that seek to destroy anything attached to it.
From past analysis, the team knew going that analogous H protein in influenza viruses is very tolerant of mutations, but the new study confirmed that the measles virus is not. Comparing two related viruses, one rigid and one flexible, in terms of evolutionary speed of surface proteins confirmed that influenza H is more open to change. The researchers reached this conclusion using a high-speed experimental technique, insertional mutagenesis, which changes all of the genes in a virus in one experiment—a useful tool to understand the future of viral evolution. They inserted mutations across the measles genome and found measles cannot survive too much change to the gene for its H protein especially.
All a flu virus H needs to attach to a target cell is to find one of the simple sugar structures that cover human cell surfaces. According to a theory supported by the current study results, this simple sugar may be better suited to binding a wider variety of viral H structures, which may account for the ability of flu H genes to constantly change without consequence. Measles H and related proteins require a specifically shaped protein receptor to attach to, which may explain why the genes for that protein, and related protein shapes, cannot change and still work.
“In theory, how different viruses evolved to attach to target cells may be a major factor driving their genetic rigidity, or flexibility, which influences the ability to tolerate the random genetic changes that are happening all the time,” said Dr. Heaton. “Both the flu and measles have historically been very successful invaders of human cells, so both rigidity and constant change genetic change have conferred value. Exactly why tradeoffs are made in viral evolution is very interesting, and the subject of ongoing studies.”
This study was funded by the National Institutes of Health. Along with Dr. Heaton, study authors in the Department of Microbiology were Benjamin Fulton, Shannon Beaty, Sohui Won and Benhur Lee and Peter Palese. The study’s second author was David Sachs of Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai.
About the Mount Sinai Health System
Mount Sinai Health System is one of the largest academic medical systems in the New York metro area, with more than 43,000 employees working across eight hospitals, over 400 outpatient practices, nearly 300 labs, a school of nursing, and a leading school of medicine and graduate education. Mount Sinai advances health for all people, everywhere, by taking on the most complex health care challenges of our time — discovering and applying new scientific learning and knowledge; developing safer, more effective treatments; educating the next generation of medical leaders and innovators; and supporting local communities by delivering high-quality care to all who need it.
Through the integration of its hospitals, labs, and schools, Mount Sinai offers comprehensive health care solutions from birth through geriatrics, leveraging innovative approaches such as artificial intelligence and informatics while keeping patients’ medical and emotional needs at the center of all treatment. The Health System includes approximately 7,300 primary and specialty care physicians; 13 joint-venture outpatient surgery centers throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and more than 30 affiliated community health centers. We are consistently ranked by U.S. News & World Report's Best Hospitals, receiving high "Honor Roll" status, and are highly ranked: No. 1 in Geriatrics and top 20 in Cardiology/Heart Surgery, Diabetes/Endocrinology, Gastroenterology/GI Surgery, Neurology/Neurosurgery, Orthopedics, Pulmonology/Lung Surgery, Rehabilitation, and Urology. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 12 in Ophthalmology. U.S. News & World Report’s “Best Children’s Hospitals” ranks Mount Sinai Kravis Children's Hospital among the country’s best in several pediatric specialties.
For more information, visit https://www.mountsinai.org or find Mount Sinai on Facebook, Twitter and YouTube.