April 22, 2026

expert reaction to Moderna / NIHR launch of new human vaccine trial: mRNA vaccine candidate against H5N1 bird flu

Scientists comment on the launch of a Moderna and NIHR mRNA vaccine candidate against H5N1 Avian Influenza.

Prof Ed Hutchinson, Professor of Molecular and Cellular Virology, MRC-University of Glasgow Centre for Virus Research, University of Glasgow, said:

“We don’t yet know what the next pandemic will be, but when it happens we will need to be able to produce large numbers of effective vaccines as quickly as possible.  The viruses that most frequently cross over from other animals into humans are the influenza A viruses, which have caused repeated pandemics in the 20th and 21st centuries.  Over the last few years a strain of H5N1 avian influenza virus has become increasingly concerning as a possible pandemic source, as it has infected animals around the world and caused numerous isolated human infections.  At this moment in time, the immediate risk of this virus to humans is low.  This is good, but it also creates a problem – the virus is constantly mutating, so our pandemic plans for H5N1 require us to be ready to prepare vaccines against a moving target.  Establishing mRNA vaccines for H5N1 could be very important in a pandemic response – partly because of the strong protective responses that these vaccines can induce but also because they can be very rapidly ‘fine-tuned’ to match a specific strain and then manufactured at scale.

“This study uses an mRNA vaccine, which provides the body with the instructions needed to make just one protein component of a virus (in this case, the ‘spike’ protein on the outside of the virus, HA, that allows the virus to bind to new cells) so that the immune system can attack this if it ever encounters a genuine infection.  This study will evaluate whether this mRNA vaccine is safe, the extent to which it causes common minor adverse reactions to vaccines (e.g. fever or pain at the injection site), and how good it is at protecting people by getting them to produce antibodies which can bind to and inactivate the virus.  (As H5N1 isn’t yet a human disease this will be tested by taking some of their blood and testing it against viruses in a laboratory.)  This ‘pre-pandemic vaccine’ trial should provide important information about whether vaccines with a similar design could be deployed in the event of an influenza pandemic.”

Prof John Tregoning, Professor of Vaccine Immunology, Imperial College London, said:

“The clinical trial described is for an mRNA vaccine against influenza.  H5N1 influenza (often called bird flu) poses a potential threat to human health in two ways.  Existing strains (if they do infect people, which fortunately is relatively rare at the moment) often cause very severe disease in humans, much more serious than the virus strains that cause influenza infections in the winter.  Secondly, most people do not have any pre-existing immunity to the H5N1 viruses – as we saw during the COVID pandemic, when people lack immunity, viruses spread faster and cause more disease.  H5N1 has been circulating in wild birds (and domestic poultry) for a number of years and there is a risk it will make the species jump to humans.  We therefore need to be prepared for this event, vaccines are a key part of this preparation.  A good comparison is seat belts, you don’t want to have to use one in an emergency, but you would be grateful that you have it if you do.  The same goes for vaccines for pandemic viruses, it is better not to have a pandemic, but if one emerges, it is better to be prepared.  One of the key lessons from the COVID was that speed of response is critical for saving lives.  Doing a large scale human vaccine trial for H5N1 now, allows for a more rapid scale up of response if the virus spreads in the future. Another lesson from the COVID pandemic was that RNA vaccines can be scaled up very rapidly, so testing this platform for this infection is a good precaution.

“Based upon the trial website (https://trials.modernatx.com/study/?id=mRNA-1018-P301 and the clinical trial registry https://clinicaltrials.gov/study/NCT07496450) this is a standard vaccine trial.  It is a phase 3 trial, which means it is testing efficacy (how protective the vaccine might be).  This is being measured as a correlate of protection, rather than showing direct protection because there is currently no H5N1 disease in people.  Influenza is a well characterised virus; historical data has provided a measurement of immune function that can be used as a correlate of protection.  This is basically a surrogate measure (a value of response) that if the volunteer goes above that level (greater than 1:40), we can assume a good degree of protection.  In the case of influenza virus, there is a scientific test called haemagglutination inhibition (or HAI).  This can be measured in human blood, if the vaccine works well, it will increase after immunisation and comparisons with previous studies can give us confidence that the vaccine will protect.

“There are 4,000 participants, with trial sites in the UK and the USA.  Participants will receive two doses of the vaccine or a placebo control.  It will evaluate the safety of the vaccine; this will be done on a sliding scale, with the highest level of scrutiny in the first 7 days after vaccination (when side effects might be most pronounced); then with continued monitoring for a month after injections for unexpected effects, with follow up for 205 days from the start.  From the information provided, this will be good quality research, the trial methodology makes sense, the sample size is large enough to detect whether the vaccine is able to induce an immune response.”

Declared interests

Prof Ed Hutchinson: “Ed Hutchinson is the Professor of Molecular and Cellular Virology at the MRC-University of Glasgow Centre for Virus Research.

Disclosures: I have received honoraria for work in a steering group of the Centre for Open Science (Open Practices in Influenza Research; 2021-2022) and on an advisory board for Seqirus (2022).  I have unpaid positions on the board of the European Scientific Working group on Influenza and other respiratory viruses (ESWI) and as a scientific adviser to PinPoint Medical.  I have received grant funding from the Wellcome Trust and UKRI, including for research on H5N1 influenza.”

Prof John Tregoning: “Prof Tregoning has previously worked with Sanofi and BioNTech on RNA vaccines for influenza.”

This Roundup was accompanied by an SMC Briefing.