H5N1 highly pathogenic avian influenza (AI) has swept through U.S. livestock farms for over a year, and for the first time, a messenger ribonucleic acid (mRNA) vaccine for dairy cows has been developed. Although further testing is needed before large-scale vaccination can be conducted, this achievement is considered significant in preventing the spread of avian influenza from livestock to humans.
◇ Efficacy confirmed in calf trials
Scientific journal Nature reported on the 20th (local time) that “while competing to find ways to contain avian influenza before it triggers a pandemic, a research team has developed the first mRNA vaccine for cattle.”
Professor Scott Hensley of the University of Pennsylvania’s School of Medicine and Dr. Amy Baker of the Agricultural Research Service (ARS) noted that “the experimental mRNA vaccine induced a strong immune response against the virus in dairy cows and showed effectiveness in preventing infections in calves,” in a paper disclosed on the 6th on the preprint server bioRxiv.
Professor Hensley stated to Nature, “These results could represent a decisive step in creating an avian influenza vaccine for livestock and reducing the risk of viruses that could cause a pandemic transmitting between animals and humans.” The results have not yet been formally peer-reviewed and published in a journal.
H5N1 avian influenza is a variant of highly pathogenic avian influenza (HPAI) that is lethal to poultry such as chickens and turkeys. The virus is named H5N1 due to its hemagglutinin (HA) and neuraminidase (NA) proteins, which are classified as type 5 and type 1, respectively. HA acts as the key to the virus binding to human respiratory cells, while NA allows the virus to exit the cell after replication.
Since the H5N1 avian influenza virus was first identified in a dairy cow on a U.S. farm in March last year, more than 1,000 herds across 17 states have been infected. There have been 66 reported cases of human infection among farm workers. In January, the first death among human infections was reported.
Concerns have grown that if the H5N1 virus transmitted from livestock infects humans, it could lead to another global pandemic following the novel virus infection (COVID-19). No human-to-human infections have been reported yet. Professor Hensley believes that to prevent a pandemic, it is essential to stop infections among dairy cows and has developed an mRNA vaccine that proved effective during the COVID-19 pandemic.
mRNA copies the virus’s genetic material to produce proteins. The COVID-19 mRNA vaccine works by injecting mRNA that makes the spike protein found on the surface of the virus into the body to induce an immune response. Professor Hensley’s research team recently replaced the hemagglutinin gene of the avian influenza virus with the genetic material of the newly discovered H5N1 virus found on dairy farms.
The research team confirmed last year that the mRNA vaccine prevents avian influenza in ferrets, which are experimental animals used to test flu vaccines. This time, they vaccinated 10 calves and fed them milk infected with H5N1 after 49 days. Scientists suspect that the H5N1 virus spread among the dairy cows through the milk. Human infections are also believed to have occurred during the milking process.
Trial results showed that vaccinated calves had significantly lower viral genetic material than unvaccinated calves, indicating that the vaccine helps suppress infections. However, there are still limitations to consider before deeming it a complete success.
Richard Webby, director of the Animal Influenza Ecology Research Institute at the World Health Organization (WHO), noted to Nature that “the transmission of avian influenza on dairy farms mostly occurred among lactating adults” and pointed out that “this study only tested the vaccine response in calves.” Professor Hensley’s research team is reportedly already conducting additional trials targeting lactating dairy cows.
◇ Vaccine for chickens and ducks also developed, conditionally approved
Other livestock vaccines are also being developed. The U.S. Department of Agriculture has approved at least seven animal clinical trials this year. Zoetis, a U.S. animal health company, announced in February that it received conditional approval from the department for an avian influenza vaccine for chickens.
Conditional approval allows for the temporary use of a drug that has demonstrated safety and similar efficacy when there are no available drugs for urgent situations. If the preventive effects are proven within a year, full approval can be obtained for actual sales.
Zoetis is the world’s leading company in the animal pharmaceuticals sector, having partitioned from the animal health division of Pfizer. It sells over 300 products, including livestock vaccines, anti-inflammatories, analgesics, feed, and nutritional supplements, in more than 100 countries. In 2020, it developed a COVID-19 vaccine for animals, which was administered to animals in zoos.
According to the WHO, H5N1 avian influenza has spread globally since 2003, infecting 950 people and resulting in 464 deaths as of last year, with a fatality rate of 49%. As avian influenza continues to spread, the government has culled infected livestock.
There are growing criticisms of the culling method that involves killing all healthy livestock near infected farms. It is considered inhumane and inefficient in disease control. Vaccines have been proposed as an alternative. While culling involves a budget of over 10,000 won per animal, which includes equipment, personnel, and compensation, vaccines are said to require only 200 won.
The issue is political. The Trump administration has taken a negative stance toward vaccines. In states where avian influenza has spread among livestock, Republican lawmakers have proposed banning the livestock mRNA vaccine, arguing that it poses health risks to humans. Scientists are concerned that the Trump administration may cut funding for mRNA vaccine development.
References
bioRxiv (2025), DOI: https://doi.org/10.1101/2025.05.01.651548
Nature Communications (2024), https://doi.org/10.1038/s41467-024-48555-z