Phase 3 Trial Launches for mRNA H5N1 Bird Flu Vaccine in UK and US

Volunteers are being recruited for a new phase 3 trial of an mRNA vaccine against H5N1 bird flu in humans, as researchers warn the virus is evolving in unexpected ways and preparing for a potential pandemic. The large trial, supported by the National Institute for Health and Care Research (NIHR) and sponsored by Moderna, is part of its UK government strategic partnership managed by the UK Health Security Agency (UKHSA). The study is also supported by Moderna's collaboration with the Coalition for Epidemic Preparedness Innovations (CEPI).

The phase 3 trial will involve around 4,000 adult volunteers aged 18 and over in the UK and USA, with 3,000 being recruited in the UK. Experts from the University of Nottingham will be delivering part of the trial from the Cripps Health Centre on the University Park Campus in Beeston in Nottingham. Nottingham will be one of 26 sites across the UK administering the vaccine.

The study aims to provide crucial evidence on whether the investigational vaccine can generate strong immune responses to protect against currently circulating and emerging strains of H5N1. This will help the UK prepare for future pandemics and apply system-wide learnings from Covid-19.

Bird flu is currently transmitted between affected birds and various mammals. While the virus does not easily spread to humans, and transmission between people is very rare, there is a risk that the virus could adapt, making it more transmissible to or between humans. Since 2024, there have been 116 confirmed human cases across the world, almost all linked to close contact with infected animals.

H5N1, first identified in Asia more than three decades ago, has evolved to infect mammalian species and spread throughout the world. Around 2020, the virus started to evolve very rapidly and began to infect mammals. In 2024, the virus was found in cattle — a surprising development because cows were not thought to be susceptible to influenza. The virus was concentrated in the cow's milk, and dairy workers became infected through contact with cow's milk.

Researchers at the University of California San Diego School of Medicine, led by a professor of pediatrics, recently published a research review in the journal Pediatrics highlighting the importance of further research on H5N1 and the possibility of human-to-human transmission. The review found that human breast tissue has receptors that can bind avian influenza. Researchers noted that pasteurization rapidly reduces viral titers in dairy milk and that H5N1 does not appear to be transmitted through consuming pasteurized milk. Pasteurizing human milk, as currently performed in the University of California Health Milk Bank for donor milk, is believed to eliminate any viable H5N1 virus.

Infections in wild animals have been documented in elephant seals, dolphins, ferrets, mink, mice, lions and tigers. Infections are now found in domestic animals such as livestock (goats and cows), domestic birds (chickens, ducks and geese), and companion animals like cats.

The Principal Investigator for the trial, a professor from the School of Medicine at the University of Nottingham, said: "We are delighted to be part of the trial of this Avian influenza vaccine, which is important to prepare the U.K. for a future pandemic."