Vaccination against the H5N1 avian flu with mRNA vaccines can protect against severe disease and death, new animal studies show.
These mRNA vaccines are similar to the Moderna and Pfizer vaccines developed to combat COVID-19. The H5N1 flu has been known to infect wild birds and poultry, with occasional spillover to humans, since the late 1990s. However, since 2021, a major outbreak of a strain that can infect many mammal species 鈥� from sea lions to cattle 鈥� has spread around the globe. The Centers for Disease Control and Prevention (CDC) have reported 66 human cases and one death. The fatality was a Louisiana man over the age of 65 who had contact with backyard poultry and wild birds.
There has not been any human-to-human spread of the H5N1 flu detected yet. But as animal-to-human infections continue to occur, researchers are preparing for the possibility of a pandemic. The new CDC study of mRNA vaccine options is one of several lines of work on mRNA and more traditional vaccines ongoing, according to study author Bin Zhou, the team lead for vaccine preparedness in the CDC鈥檚 influenza division.
Above: Avian flu can have devastating consequences in densely packed poultry farms. Now, mRNA vaccines have shown promise in protecting against illness in animals subjected to H5N1 avian flu.
Many older vaccine manufacturing methods involve a step of growing viruses inside eggs. But eggs are already in short supply due to the avian flu infecting poultry farms, and eggs can be contaminated by the flu virus itself. There are cell-based vaccine manufacturing techniques that sidestep these problems, but mRNA is promising because of the relative speed with which vaccines can be produced and updated against mutated strains.
鈥淲e think the mRNA vaccine provides us another platform which can be very useful to protect the public if there is a need to use a vaccine,鈥� Zhou says.
mRNA development steps
The first step in developing these mRNA vaccines is determining which antigen 鈥� or molecule on the virus鈥� surface 鈥� the vaccine should target for best results. The H5 hemagglutinin is the protein that H5N1 uses to enter and infect cells. Secondarily, vaccines could also target neuraminidase (NA), an enzyme that helps viruses leave the host cell after infecting it.
Zhou and his team tested five different combinations of H5 and NA, with varying modifications to the antigens and at various doses, in ferrets. They then monitored the ferrets for antibodies, proteins that bind to antigens and mark them for destruction by the immune system. This first phase of experimentation showed that using an unmodified H5 hemagglutinin from the virus currently circulating was just as effective as any combination of modifications. Adding NA did not boost the response, either.
Similar to the mRNA COVID-19 vaccines, these influenza mRNA vaccines led to a spike in antibodies, then a quick decline. A booster shot five weeks later brought the antibody levels back up, and though they declined again, the drop was not as steep, and the protection remained stable for months. A third dose five months later boosted antibodies again, but not as much as the second dose.
The team then tested a pared-down group of vaccines on a larger group of animals 鈥� ten per vaccine, plus a control. The animals got two doses of the vaccine and then were exposed to a lethal amount of H5N1 virus.
Vaccination protected ferrets against severe disease and death. While all animals in the unvaccinated group died or had to be euthanized by day 9 of the study, only one of the vaccinated animals became severely ill and had to be euthanized. Vaccinated animals also showed lower viral loads everywhere from the nose and the trachea to the lungs and intestines.
鈥淭he vaccine is not 100% protective, even in animal studies,鈥� Zhou claims. 鈥淏ut compared to the unvaccinated ferrets, it鈥檚 really very good protection.鈥�
The researchers then took blood serum 鈥� the portion of the blood not including the red blood cells 鈥� from the ferrets. They mixed this serum, which is rich in immune cells and antibodies, with virus taken from a patient in Texas who contracted the flu from contact with cattle. The serum successfully killed the virus.
There are a lot more steps ahead, Zhou adds, including human trials. The research is happening within and outside of the CDC. For example, Arcturus Therapeutics, a San Diego-based vaccine company, received Food and Drug Administration (FDA) clearance in November for Phase 1 trials to test the safety and immunogenicity of an H5N1 mRNA vaccine. Pharmaceutical company CureVac started Phase 1 trials in April 2024 and GSK acquired the full rights to the vaccine candidate in July 2024. And mRNA giant Moderna received $176 million from the U.S. Dept. of Health and Human Services in July to develop an H5N1 vaccine.
Importance of getting vaccinated
Whether or not widespread H5N1 vaccination is ever needed, Zhou urges individuals to take advantage of the seasonal flu vaccine. If someone is unfortunate enough to contract both seasonal flu and the avian H5N1 flu at the same time, those viruses have the potential to swap genetic material within that person鈥檚 cells, potentially enabling H5N1 to gain mutations that allow it to pass more easily from person to person, Zhou adds.
鈥淚f you are taking the seasonal flu vaccine, you will reduce your chance of getting seasonal flu,鈥� he says, 鈥渁nd you will reduce the chance that you serve as a reservoir for the two viruses to mix.鈥�
Hatta, M., et al., 鈥淎n Influenza mRNA Vaccine Protects Ferrets from Lethal Infection with Highly Pathogenic Avian Influenza A(H5N1) Virus,鈥� Science Translational Medicine, doi: 10.1126/scitranslmed.ads1273 (Dec. 18, 2024).
This article originally appeared in the Update column in the February 2025 issue of CEP. Members have access online to complete issues, including a vast, searchable archive of back-issues found at www.aiche.org/cep.