Avian Influenza (H5N1) Vaccines: What's the Status?
Vaccines are some of the best tools to prevent widespread and severe disease caused by influenza viruses. Understanding how well existing influenza vaccines work against circulating H5N1, as well as developing new options, is critical for ensuring we are prepared in the event of a broad H5N1 outbreak.
Are There Existing H5N1 Vaccines?
The U.S. licensed 3 H5N1-focused vaccines in 2007, 2013 and 2020; additional vaccines have been authorized by the European Medical Association (EMA) for protection against various H5 influenza viruses. The target population for these vaccines—and H5N1 vaccines overall—is not the general public, but rather those with the highest risk of exposure to the virus (e.g., people who work with poultry or cattle). Finland is currently the only country offering a vaccine to high risk individuals. Other countries, including Canada and the U.S., have stockpiled vaccines that could be distributed if or when needed, or have historically offered H5N1 vaccination to those at high risk of infection (e.g., Taiwan in 2013).
The U.S. also harbors stockpiles of influenza A vaccine "building blocks"—i.e., antigens and adjuvants, which trigger and enhance an immune response, respectively. Managed by the Biomedical Advanced Research and Development Authority (BARDA), the National Pre-pandemic Influenza Vaccine Stockpile (NPIVS) contains the materials (e.g., influenza A H5 antigen) to quickly advance production of H5N1 vaccines that closely match circulating viruses.
The World Health Organization (WHO) maintains a list of all candidate vaccines for H5N1 and other zoonotic influenza viruses, which it updates as part of its twice-yearly consultations on influenza vaccine composition (the same meetings in which the seasonal vaccine composition recommendations are debated).
How Effective Are Licensed H5N1 Vaccines?
Existing, licensed vaccines target H5N1 viruses that differ from the clades/strains than are circulating in 2024-2025. The EMA-authorized vaccine being administered in Finland is an exception. The vaccine manufacturer, CSL Sequiris, signed an agreement to provide over 660,000 doses to the European Union to support pandemic preparedness.
In the influenza world, a clade is a group of viruses that share genetic similarities in their hemagglutinin (HA) surface glycoproteins—the part of the virus that vaccines primarily train the immune system to recognize. While different clades of H5N1 have the same HA subtype (H5), genetic variations set them apart from one another. Viruses within a clade can be further subdivided into strains, based on additional genetic changes. Collectively, these differences may impact immune responses to the virus.
With that in mind, if licensed H5N1 vaccines were deployed today, would they still offer protection?
Yes, to an extent. In a recent study, individuals who were vaccinated with 1 of 2 of the licensed H5N1 vaccines generated cross-reactive binding and cross-neutralizing antibodies against clade 2.3.4.4b virus (the dominant type spreading in 2024-2025). Participants exhibited seroconversion rates (i.e., demonstrated antibodies against H5N1) of 60-95%, suggesting that the stockpiled vaccines could be good stand-ins as new vaccines become available. In the event of a pandemic, viral strains in licensed vaccines could be changed to reflect circulating viruses, similar to how seasonal flu vaccines are updated each year. Moreover, different vaccines could be “mixed and matched” across doses to evoke an antibody response that is even broader than a single vaccine could achieve on its own.
What Vaccines Are Being Developed?
Researchers are developing completely new vaccine options as well. Different types of vaccines (e.g., mRNA, whole inactivated virus, live-attenuated virus, among others) stimulate the immune system in different ways, and rely on different manufacturing tools and processes. With that in mind, mRNA vaccines, first rolled out in in response to the COVID-19 pandemic, are particularly attractive for pandemic preparedness. They are among the fastest vaccines to make and can be easily altered to match circulating viral strains. Investigations into the use of mRNA vaccines against H5N1 have shown promising results.
For example, 2 doses of an mRNA vaccine derived from a clade 2.3.4.4b H5N1 virus protected ferrets (the most common model for studies on influenza infection and disease) from lethal doses of H5N1—animals who did not receive the vaccine died. It also reduced viral titers in the upper and lower respiratory tracts, which is important for reducing disease severity and risk of viral transmission. Another study similarly showed that an mRNA vaccine encoding the HA protein from a clade 2.3.4.4b H5 isolate prevented morbidity and mortality in ferrets after challenge with H5N1.
Clinical trials are also underway. Arcturus Therapeutics, a commercial mRNA medicines company, began a Phase 1 trial in December 2024 evaluating the safety and immune response of their self-amplifying H5N1 mRNA vaccine. The vaccine contains mRNA encoding viral glycoproteins (HA and neuraminidase, or NA, the other major glycoprotein decorating influenza viruses), as well as proteins that help make more of the viral mRNA in the body. This strategy reduces the vaccine concentration needed for administration and boosts antigen exposure. Moderna is preparing for a Phase 3 trial with their mRNA vaccine candidate targeting H5 and H7 avian influenza viruses, the latter being another influenza A subtype found in birds with the potential to infect humans. In January 2025, the Department of Human Health Services issued a $590 million contract to Moderna to accelerate vaccine development (though the future of that contract is hazy).
Developing Livestock Vaccines
Humans are not the only targets for vaccine development. Agricultural value and close ties between animals and people in driving the spread and evolution of H5N1 necessitates protecting at-risk animals who are in close contact with humans (e.g., poultry, dairy cows). Historically, disease control in these animal populations has relied on euthanasia, due to concerns that imperfect protection from a vaccine may lead to undetected viral spread, resulting in international trade limitations that restrict cross-border movement of vaccinated poultry.
Nevertheless, a few countries, like China and France, do vaccinate poultry against H5N1. While the U.S. is not currently vaccinating poultry, as of February 2025, the U.S. Department of Agriculture (USDA) was planning to invest $100 million toward innovations in poultry vaccines. To that end, the agency recently granted a conditional license to Zoetis, a global animal health company, for an updated poultry vaccine targeting H5 influenza outbreak strains. The USDA had stockpiled an older version of the Zoetis vaccine from 2016-2021, though the doses were never used. The updated vaccine contains a heat-killed variant of an H5N2 virus, which, by virtue of similarities in its HA protein, elicits protective immunity against circulating H5N1. Vaccines for cows are also under development, with at least 7 candidates approved for field safety trials.
It is worth highlighting that the information and advancements outlined above are current as of this writing. In a rapidly evolving political landscape, in which disruptions in research and public health funding and the U.S. response to bird flu in general have already occurred, it is unclear how the development and distribution of H5N1 vaccines will be affected.
Do Seasonal Flu Vaccines Work Against H5N1?
Not exactly. Seasonal flu vaccines are designed to spark immunity against influenza strains spreading widely among humans. Each year, the targets are variants of H1N1 and H3N2 influenza A viruses (plus influenza B), which have been dominant in the human population for over 50 years. As mentioned, influenza vaccines primarily help the immune system learn to recognize and respond to HA glycoproteins. This means that a vaccine targeting H1N1 or H3N2 may not be robustly protective against H5N1, which has a different HA subtype.
That isn’t to say there is no protection at all. One study suggested that the similarity between the NA subtype shared by H5N1 and seasonal H1N1 viruses, as well as the “stalk” component of HA (the bottom half of the protein, which tends to be less variable than the top) means there is likely “a degree of pre-existing immunity” in humans that could “blunt the severity of human H5N1 infections.”
The key point is that seasonal flu vaccines are not a reliable preventive tool against H5N1. In theory, strains of H5N1 could be incorporated into seasonal vaccines, though this would require regulatory approval and widespread H5N1 transmission among humans. Developing a universal flu vaccine encompassing diverse influenza subtypes could also offer protection against H5N1 down the line.
Getting a flu vaccine right now is still important, though. Doing so reduces the chances of someone becoming infected with both a seasonal influenza strain and an H5N1 strain. If this were to happen, the viruses could swap genetic material in a process known as reassortment. Such genetic shuffling increases the risk of a virus acquiring mutations that promote its transmissibility to new species and increase disease severity. For example, the H1N1 virus that caused the 2009 flu pandemic, which resulted in roughly 60 million cases in the U.S. alone, emerged after a reassortment event in pigs. Seasonal flu vaccines can help prevent humans from similarly becoming influenza mixing pots.
How to Protect Against H5N1 Infection
As future H5N1 vaccines take shape, there are steps people can take to protect themselves against H5N1 in the interim.
In general, avoiding ill or dead animals is a good idea. People who are around sick or dead animals (e.g., wild birds, poultry and other wild or domesticated critters), animal feces, litter or other potentially contaminated material should wear safety goggles, disposable gloves, N95 masks and other personal protective equipment (PPE). Though the risk posed by pasteurized eggs and milk is low, it is also recommended people cook eggs to a safe internal temperature (165ºF/74ºC); unpasteurized (raw) milk is more readily contaminated and should be avoided. Poultry and livestock owners or workers, who have a greater risk of exposure, can take additional steps to protect themselves.
In all cases, if one develops symptoms associated with the disease (e.g., sore throat, eye redness and cough), especially after contact with ill or potentially ill animals, they should contact a health care provider right away.
ASM is committed to broadly disseminating research relevant to outbreaks of concern. Browse the ASM Journals Avian Influenza Virus Article Collection for new insights on the clinical implications of the virus, its impacts on the food supply chain and more.
