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Could targeting STING make a universal flu vaccine?

In animal tests, vaccine gives broad protection

by Laura Howes
February 21, 2020


Each year, between 3 and 5 million people get severe flu infections and hundreds of thousands die. The key to the virus’s persistence is its constant evolution. Since influenza is constantly changing, people need get vaccinated every year—and even then the vaccine they get might not protect them against all of the different strains of flu that have emerged since the vaccine’s formulation.

Structure of full-length chicken STING bound to cGAMP.
Credit: Nature
This cryo-EM structure shows how an molecule called cGAMP (purple) binds to the STING protein.

It’s therefore no surprise that many flu experts say we need a universal flu vaccine that will work against multiple strains and not be outwitted by evolution. But making one is extremely challenging. Now, a group of researchers at Harvard Medical School and Fudan University have tried a different approach to the problem. Instead of focusing on the antigen, the main part of the vaccine, they turned to an often overlooked part of vaccine formulation. They made a new adjuvant, an immune system kickstarter, that boosts an inhaled flu vaccine by activating the important immune protein STING. This protein, a stimulator of interferon genes, is a popular target for cancer treatment but was originally identified because of its role in antiviral immunity. Tests in mice showed that the boosted vaccine gives immunity against multiple strains (Science, 2020 DOI: 10.1126/science.aau0810).

Vaccines protect the body against infection by exposing the immune system to key parts of the virus so that some of the immune system’s cells will remember the infection and surge into action when they encounter the live virus. To make that process more effective, vaccine formulations can also use adjuvants to boost the immune system’s response.

At Harvard, Mei X. Wu’s group had already shown that cGAMP, a chemical that triggers the STING protein, could be, in her words, an “ideal” adjuvant for dermal flu vaccines. But what about nasal spray flu vaccines, which are often given to children? To deliver the cGAMP into lung cells, the researchers needed to encapsulate them in a negatively charged nanoparticle made of lipids that are taken up my cells in the lungs. When mice inhaled the vaccine boosted with cGAMP containing nanoparticles, the immune response of the mice was sped up and the mice became protected against multiple flu strains.

The work is an unconventional way of overcoming the problems of the flu vaccine, says Susanne Herold, an expert in pulmonary infections at the University Hospital of Giessen and Marburg. She says more work will be needed to show that STING activation can help protect humans and suggests that the most effective approach may be to combine these nanoparticles with other potential universal flu vaccines to create the solution that we urgently need.



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