A major human trial for a bird flu vaccine has begun in the UK, marking a significant step in global efforts to prepare for a potential influenza pandemic. The Phase 3 study, involving around 4,000 volunteers across the UK and United States, will test an mRNA vaccine developed by Moderna against the evolving A(H5N1) strain of avian influenza.
The Trial Launch and Its Participants
The trial, sponsored by Moderna and supported by the UK’s National Institute for Health and Care Research (NIHR), aims to recruit approximately 3,000 participants in the UK at 26 sites across England and Scotland, with half of those volunteers aged over 65. A further 1,000 will be recruited in the US. The study is actively encouraging poultry farmers and people with close contact with birds to sign up, reflecting the virus’s primary transmission route from animals to humans. Participants will receive two doses of the vaccine, called mRNA-1018, three weeks apart, with the study set to run for seven months.
Dr Rebecca Clark, the trial’s national co-ordinating investigator based at Layton Medical Centre in Blackpool, said the work was a “proactive attempt” to shield against the possibility of human-to-human transmission. “We know that the A(H5N1) strain is evolving and spreading across animal species, and though it does not yet move easily between humans, we have to treat human-to-human transmission as a real possibility,” she stated. The trial’s design, using community clinics rather than traditional hospital settings, is intended to ensure research can be carried out across a range of locations and populations.
The mRNA Technology at the Heart of the Vaccine
The vaccine at the centre of this large-scale trial utilises messenger RNA (mRNA) technology, a platform that proved its speed and efficacy during the Covid-19 pandemic. Unlike traditional vaccines, which often use a weakened virus or viral proteins, mRNA vaccines work by instructing the body’s own cells to produce specific, harmless proteins from the target virus. In this case, the mRNA-1018 jab trains the immune system to recognise proteins from the A(H5N1) virus, priming it to mount a rapid and effective defence if it later encounters the actual pathogen.
According to Dr Hiwot Hiruy, senior director of clinical development at Moderna, early Phase 1/2 trials involving about 1,200 participants found the jab to be “generally well tolerated, with most of the side-effects being mild to moderate, and there were no safety concerns.” She added that the vaccine induced a strong immune response detectable as early as seven days after the first injection. A key advantage of the mRNA platform, Dr Hiruy noted, is that vaccines can be produced faster and adjusted rapidly to match new viral strains compared to traditional technologies—a critical asset in a fast-moving outbreak.
The Coalition for Epidemic Preparedness Innovations (CEPI) is providing up to $54.3 million to support this Phase 3 trial and, as part of its agreement with Moderna, the company has pledged to allocate 20% of its H5 pandemic vaccine manufacturing capacity for timely, affordable supply to low- and middle-income countries should the vaccine be licensed.
Pandemic Preparedness in the Face of an Evolving Threat
The launch of this trial is a cornerstone of the UK’s and global strategy to bolster defences against a virus considered a top pandemic threat. The A(H5N1) strain first emerged in southern China in 1996, with the first human infections recorded a year later. Since 2003, highly pathogenic H5N1 viruses have caused a significant number of human deaths globally, with a case fatality rate of around 50% in reported cases. While the current risk to the UK public is assessed as “very low” by the UK Health Security Agency (UKHSA), the virus’s behaviour is causing deep concern.
It has caused a global panzootic in birds and has increasingly spilled over into mammals, including mink, marine mammals, and, notably in 2024, dairy cows in the United States. Since the start of 2024, there have been 116 confirmed human cases worldwide, almost all linked to close contact with infected animals. The UK has recorded its own human cases, with a symptomatic case in January 2022 and another in January 2025, both linked to infected birds on farms. No human-to-human transmission has been documented in Britain or Europe.
Dr Richard Pebody, director of epidemic and emerging infections at UKHSA, which manages the government’s strategic partnership on this trial, stated: “We clearly don’t know when the next pandemic is going to be… but what we do know is that a flu pandemic is the most likely future pandemic.” He emphasised that while the risk remains low, the virus “continues to evolve,” and the agency remains alert to the potential for person-to-person spread.
This mRNA trial complements existing UK preparedness measures. At the end of 2024, the government announced it had secured a contract for more than five million doses of an H5 influenza vaccine for its stockpile, though that jab uses more traditional technology. The current trial is part of the UK Vaccine Innovation Pathway, designed to expedite vaccine development. Moderna proceeded with this Phase 3 study despite the US government ending a separate contract for pandemic influenza vaccine work, underlining the importance of alternative funding from bodies like CEPI.
