Vaccination against influenza remains a key public health challenge, in large part because the virus changes every year. The surface of influenza viruses are coated with a protein called hemagglutinin (HA), which helps the virus bind to cells in our body. HA has two main regions: a “head” region, which mutates very rapidly, and a “stem” region, which tends to stay the same. The head region of HA is easier for immune cells to access, so most antibodies (immune molecules that can help fight viruses) against influenza target this region. The typical flu vaccine helps the body develop these antibodies, and must be updated year to year as the head region mutates. However, researchers from MIT and the Ragon Institute are working on a new, universal flu vaccine that helps the immune system instead target the more stable stem region.  

The researchers developed a computational model to predict how factors like protein geometry and binding strength impact which region of the HA protein antibodies bind to. They used this model to help them design a nanoparticle-based vaccine coated with the stem region of HA. In mice engineered to express human-like antibodies, treatment with this vaccine led to the production of antibodies targeting the stem region that are effective against many different flu virus strains. Most adults have some pre-existing antibodies against influenza, whether from vaccination or prior infection. The researchers think that this nanoparticle vaccine could help selectively boost HA-stem specific antibodies in such cases, which would broadly improve and expand immunity to influenza. 

An important next step for this research will be to show that these HA-stem specific antibodies are sufficient to protect against influenza infection in animal models, and hopefully in humans as well. If it works, a vaccine like this could mean that instead of getting a new flu vaccine every year, we could get just one or two doses and have long-lasting immunity against many different influenza strains. By fine-tuning the antibody response, these researchers may have discovered a way to improve protection against both seasonal and pandemic flu. 

Lead Author Assaf Amitai is a Research Scientist at the Massachusetts Institute of Technology. Daniel Lingwood is an Assistant Professor of Medicine at Harvard Medical School and a group leader at the Ragon Institute of MGH, MIT, and Harvard. Arup Chakraborty is the Robert K. Haslam Professor of Chemical Engineering at MIT, a core member of the Institute of Medical Engineering & Science at MIT, and a founding steering committee member of the Ragon Institute. 

Managing Correspondent: Jaclyn Long

Original article: Defining and Manipulating B cell Immunodominance Hierarchies to Elicit Broadly Neutralizing Antibody Responses Against Influenza Virus

Press articles: A step toward a universal flu vaccine

Universal Influenza Vaccine Designed by MIT Researchers

Image credit: stock illustration ID: 793375252 by Kateryna Kon

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