Graphical description of a virus.
Expand / Influenza virus displays H and N proteins on its surface.

An mRNA-based flu vaccine designed to provide long-lasting protection against a variety of influenza viruses is now in phase 1 clinical trials. The National Institutes of Health announced this week.

The trial brings the remarkable success of the mRNA vaccine platform to the long-term effort to develop a universal flu vaccine. Currently, health systems around the world fight the seasonal scourge of bullets that must be adjusted to keep up with the ever-changing strains. This update takes place months before a normal distribution, which gives producers time to produce in quantity, but also provides opportunities for the transfer of stress to change unexpectedly. If the shot of the year is not a good match for the strains circulating in a given season, the effectiveness of infection can be disastrous. Still, even when the shot matches well, people need another shot the next year.

“Universal influenza vaccination is a major public health achievement, eliminating the need for both annual boosters of seasonal influenza vaccines and the need for patients to receive the flu vaccine each year,” the National Institute of Allergy and Infectious Diseases said in a news release. Universal flu vaccination can serve as an important line of defense against future flu outbreaks.”

A successful design was very difficult. Flu vaccines usually elicit an immune response to the fast-growing proteins outside the flu virus particles, hemagglutinin (A or H) and neuraminidase (NaO or N). These proteins are responsible for helping the virus enter and exit human cells, respectively, during infection. Both proteins stick to the outside of the virus and look like lollipops, the ends of which have evolved and are prime targets for antibodies that protect against the virus.

For global vaccine design, the NIH researchers targeted not the top of these proteins, but a portion of the Ha protein stem—the part of the protein that doesn’t change rapidly. Human antibodies targeting this conserved region target Ha proteins from different influenza strains of the same class. And since this part is not quickly, the vaccine can cause long-term immunity. In this design, an mRNA-based vaccine includes a fragment of the genetic code in the form of mRNA that provides human cells with a blueprint for this conserved stem region. From this, the immune system can learn to target it.

It already exists. Information that suggests that this target can work. Before using the mRNA-based design, NIH researchers developed a similar HA-stem-targeted vaccine that was safe and effective in a Phase I trial. The vaccine uses fragments of the Ha-stem stable protein attached to a nanoparticle. Last month, NIH researchers published results showing that this nanoparticle vaccine induced protective antibodies against influenza viruses from the same virus group (H1). And these antibodies stuck around for more than a year after vaccination. The vaccine candidate has moved on to a second trial. The researchers hope that having more platforms in the works will increase their chances of finding a successful vaccine.

For now, the mRNA-based vaccine will begin with a small trial of 50 people recruited by partners at Duke University. Three groups of 10 volunteers will receive different doses of the vaccine to find the optimal dose. Once this is achieved, 10 additional vaccinations are given, and their responses are compared to a control group of 10 people who receive the standard annual flu vaccine.

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