It was roughly a year after the earliest cases of covid-19 before the first vaccines against the SARS-CoV-2 virus were ready for roll-out. By then millions had died worldwide and economies were devastated. In the advent of a bird flu pandemic, we will be able to react more rapidly, because we should have an mRNA vaccine already approved and ready to go. A phase III trial of a such a vaccine is now getting under way in the UK and the US.

“A flu pandemic is the most likely future pandemic. And it’s really critical that we ensure we’re properly prepared,” says Richard Pebody at the UK Health Security Agency.

The main threat is a strain of H5N1 bird flu called clade 2.3.4.4b. It has spread globally in wild birds since evolving around a decade ago, even reaching the Antarctic. Many wild mammals have been infected by wild birds and it has often spread to poultry farms. In the US, it has been circulating in dairy cattle.

There have been more than 100 human cases since 2024, although so far there is no evidence of the virus spreading from person to person. But as long as H5N1 bird flu keeps circulating, the risk will remain.

“We cannot predict the timing or the severity of the next pandemic. However, with continued circulation of influenza viruses in animal populations, and the potential for virus adaptation, preparedness remains essential,” says Hiwot Hiruy at Moderna.

The company’s mRNA-1018 vaccine against H5N1 bird flu has already undergone phase I and II trials, with no safety concerns found. Now a phase III trial that will involve 3000 volunteers in the UK and 1000 in the US is starting.

Normally trials measure the effectiveness of vaccines directly, but since H5N1 bird flu isn’t spreading among people, the trial will instead look at the strength of the immune response in the volunteers. The results of the earlier trials suggest the vaccine evokes a strong response, says Hiruy.

The trial is prioritising people aged over 65 and people who work with poultry, as they are most at risk from bird flu.

Some countries do already have stockpiles of conventional vaccines against H5N1 bird flu. For instance, the UK has 5 million doses. But this existing vaccine is made using chicken eggs, like many vaccines against the seasonal flus circulating in people. With this technique, it is very difficult to rapidly scale up production or make changes to the vaccine if viruses evolve significantly.

By contrast, mRNA vaccine production can be rapidly scaled up and it’s very easy to change the vaccine should that prove necessary. So mRNA vaccines have major advantages when it comes to pandemic preparation, says Pebody.

The trial is being funded by the Coalition for Epidemic Preparedness Innovations (CEPI), which is backed by more than 30 countries and other organisations. CEPI stepped in after the US government cut funding for mRNA vaccines.

Countries such as the UK and the US may also roll out H5N1 vaccines for farm animals, especially poultry. This approach has long been used in some other countries, with a study in France finding that vaccinating ducks dramatically reduced H5N1 outbreaks on farms.