Avian influenza, commonly known as bird flu, has a long and devastating history, significantly impacting human and animal populations alike. The 1918 influenza pandemic, caused by an H1N1 virus with avian origins, resulted in the deaths of over 50 million people worldwide, highlighting the catastrophic potential of such viruses. Fast forward to today, the highly pathogenic avian influenza strain H5N1 has been causing a global animal pandemic since its emergence in 1996, though human infections have remained relatively rare.
H5N1 has led to the deaths of billions of poultry birds and millions of wild birds, and it has infected at least 48 species of mammals. In the United States, this strain has been detected in various mammals, including farm cats that died after consuming unpasteurized milk from H5N1-infected cattle. This development has sparked significant concern among scientists and public health officials, who are now more alert than ever.
The virus’s ability to jump from mammal to mammal, including cattle, has raised alarms. In March, H5N1 was found to be spreading among cattle, and by April, a farm worker in Texas contracted the virus from a cow, marking the first known case of such transmission. Modern cattle farming practices, with large, densely packed herds, provide a fertile ground for the virus to mutate and potentially enhance its ability to infect humans.
While human-to-human transmission of H5N1 has been limited and non-sustained, the virus’s high mortality rate of over 50% in infected individuals is alarming. Since 2003, 463 people have died from H5N1, underscoring the severe threat it poses. However, a significant shift in the virus’s transmission dynamics, particularly if it becomes more adept at spreading among humans, could necessitate urgent public health interventions, including the development and distribution of a human vaccine.
The World Health Organization (WHO) has not yet deemed it necessary to develop a human vaccine for H5N1, given the current state of the virus. However, the organization has systems and plans in place to rapidly respond should the situation change. Maria Van Kerkhove, an epidemiologist and interim director of epidemic and pandemic preparedness and prevention at WHO, emphasizes that the virus’s ability to infect new species alters our understanding of its behavior and potential risks. Herd-to-herd transmission among cattle in the US is being closely studied to understand the virus’s circulation patterns.
Table 1. Global reported A(H5N1) human cases, January 2022 through April 25, 2024
| Cambodia | February 2023 | Critical illness, died | Clade 2.3.2.1c |
|---|---|---|---|
| February 2023 | Mild illness | Clade 2.3.2.1c | |
| October 2023 | Critical illness, died | Clade 2.3.2.1c | |
| October 2023 | Critical illness, died | Clade 2.3.2.1c | |
| November 2023 | Critical illness, died | Clade 2.3.2.1c | |
| November 2023 | Mild illness | Clade 2.3.2.1c | |
| January 2024 | Severe illness, survived | Clade 2.3.2.1c | |
| January 2024 | Severe illness, survived | Clade 2.3.2.1c | |
| January 2024 | Critical illness, died | Clade 2.3.2.1c | |
| February 2024 | Severe illness, survived | Not reported | |
| February 2024 | Asymptomatic | Clade 2.3.2.1c | |
| Chile | March 2023 | Critical illness, survived | Clade 2.3.4.4b |
| China | September 2022 | Critical illness, died | Clade 2.3.4.4b |
| January 2023 | Severe illness, outcome not reported | Clade 2.3.4.4b | |
| Ecuador | December 2022 | Critical illness, survived | Clade 2.3.4.4b |
| Spain | September 2022 | Asymptomatic | Clade 2.3.4.4b |
| October 2022 | Asymptomatic | Clade 2.3.4.4b | |
| United Kingdom | January 2022 | Asymptomatic | Clade 2.3.4.4b |
| May 2023 | Asymptomatic | Clade 2.3.4.4b | |
| May 2023 | Asymptomatic | Clade 2.3.4.4b | |
| July 2023 | Asymptomatic | Clade 2.3.4.4b | |
| July 2023 | Asymptomatic | Clade 2.3.4.4b | |
| United States | April 2022 | Mild illness (fatigue) | Clade 2.3.4.4b |
| March 2024 | Mild illness (conjunctivitis) | Clade 2.3.4.4b | |
| Vietnam | October 2022 | Critical illness, survived | Not reported |
| March 2024 | Critical illness, died | Clade 2.3.2.1c |
Since 1997, a total of 909 sporadic human A(H5N1) cases have been reported from 23 countries, caused by different HPAI A(H5N1) virus clades [24,25], with a cumulative case fatality proportion of greater than 50%. Human A(H5N1) cases peaked in 2006 (115 cases, 9 countries) and 2015 (145 cases, 4 countries) primarily due to a large epidemic in Egypt with 136 cases [Figure 1].
Nearly all reported human A(H5N1) cases had poultry exposures, such as to sick or dead poultry or visiting live poultry markets. Rare, limited, and non-sustained instances of human-to-human HPAI A(H5N1) virus transmission likely occurred in a small number of family members following prolonged, close unprotected exposure with a symptomatic case-patient during 2004-2007 in multiple countries [26-29].
The presence of H5N1 in milk, particularly unpasteurized milk, is another significant concern. Researchers are investigating the role of pasteurization in inactivating the virus, emphasizing the importance of consuming only pasteurized milk products to mitigate the risk of infection.
The process of producing and rolling out a human vaccine for bird flu would involve several steps and systems already in place. Unlike the novel SARS-CoV-2 virus, which led to the COVID-19 pandemic, influenza viruses have been studied for over 70 years through the Global Influenza Surveillance and Response System (GISRS). This global partnership includes 150 national influenza centers in 130 member states, including 12 centers specific to H5. These centers monitor the circulation of influenza viruses to identify subtypes with epidemic or pandemic potential.
Additionally, the Pandemic Influenza Preparedness (PIP) framework works alongside GISRS to identify candidate vaccine viruses, facilitating the early production of vaccines. Several H5N1 vaccines are already in development under this framework. Scaling up vaccine production would require a declaration from WHO that the virus has pandemic potential. This would activate agreements to shift production from seasonal influenza vaccines to pandemic vaccines.
Vaccine manufacturers are prepared to respond to a significant mutation of H5N1 that could enhance its transmissibility among humans. Historical surveys on H5N1 exposure indicate that those most at risk are individuals directly exposed through occupations involving contact with poultry. However, the global population could be largely susceptible to this virus if it adapts for more efficient human transmission.
Existing vaccines for avian influenza do not utilize the same messenger ribonucleic acid (mRNA) technology that was used for COVID-19 vaccines. Instead, they rely on traditional egg-based manufacturing processes. This involves injecting candidate vaccine viruses into fertilized eggs, incubating them for virus replication, and then harvesting the fluid. While this process is slower, the infrastructure for influenza vaccine production is well-established, with estimates suggesting that four to eight billion doses of a pandemic influenza vaccine could be produced over a 12-month period.
Through the PIP framework and agreements with vaccine manufacturers, WHO would have immediate access to about 11-12% of this production, equating to approximately 500 million doses, although this number could vary based on antigen requirements.
The rollout of a potential avian influenza vaccine could be faster than the COVID-19 vaccines due to the preparedness and existing systems in place. Identifying H5N1 candidate vaccine viruses and having a manufacturing pipeline ready positions the global health community to respond swiftly if needed. The prioritization for vaccine distribution would likely focus on those most at risk of exposure and severe disease, such as healthcare workers, young children, pregnant women, and individuals with underlying health conditions.
The comparison with the COVID-19 vaccine rollout highlights the advantages of having established systems for influenza surveillance and vaccine production. While COVID-19 vaccines took about a year to be widely used, a potential avian influenza vaccine could be available earlier due to the preparedness of global health systems.
H5N1 Bird Flu in US Cattle and Milk: Swift Response and Vaccine Preparedness Initiatives by Health Authorities
The widespread presence of H5N1 bird flu in US cattle and milk continues to raise significant concerns, prompting swift action from health authorities and vaccine scientists. The Assistant Secretary for Preparedness and Response (ASPR) at the US Department of Health and Human Services (HHS) has announced a proactive step in pandemic preparedness by planning to produce 4.8 million doses of H5N1 avian flu vaccine.
Dawn O’Connell, JD, a key figure in this initiative, stated that health officials have identified a manufacturing line at one of their partners dedicated to the fill-and-finish steps of vaccine production. This strategy ensures that the production of the seasonal flu vaccine remains uninterrupted. Currently, the H5N1 vaccine exists in bulk form and will be processed into multidose vials, a step that takes a few months but ultimately saves critical time if rapid deployment becomes necessary. Federal health officials have confirmed that one of the two H5N1 candidate vaccine viruses is well-matched to the circulating strain, providing a robust foundation for this preparedness effort.
Federal agencies are actively discussing the key triggers that would necessitate the deployment of H5N1 vaccine doses. These discussions include potential changes in the virus’s transmission dynamics, such as an increase in human-to-human transmission, which would significantly elevate the risk of a pandemic. Nirav Shah, MD, JD, the principal deputy director at the Centers for Disease Control and Prevention (CDC), emphasized that changes in transmission propensity, increased severity of illness, and cases appearing in individuals without epidemiological links to affected dairy farms are all critical factors being monitored.
Shah also highlighted the importance of vigilance for mutations in the virus, which could alter its behavior and threat level. These ongoing discussions across federal agencies underscore the importance of a coordinated response to emerging infectious diseases.
The potential involvement of mRNA vaccine makers Pfizer and Moderna in H5N1 vaccine development is another promising avenue. Discussions are underway to determine how these companies, which played a pivotal role in developing COVID-19 vaccines, might contribute to the avian flu vaccine effort. An announcement regarding their involvement is expected soon, which could further enhance the preparedness and response capabilities for H5N1.
The production and potential deployment of the H5N1 vaccine are part of a broader strategy to mitigate the risks associated with avian influenza. The global surveillance and response systems in place, such as GISRS and PIP, provide a strong framework for monitoring influenza viruses and facilitating vaccine development. These systems ensure that health authorities can rapidly respond to changes in the virus’s behavior and threat level.
The proactive steps taken by US health authorities highlight the critical importance of preparedness in the face of emerging infectious diseases. The identification of a manufacturing line for the fill-and-finish steps of the H5N1 vaccine, the ongoing discussions about deployment triggers, and the potential involvement of mRNA vaccine makers are all vital components of this comprehensive preparedness strategy.
As the situation evolves, continuous monitoring and collaboration across federal agencies, international organizations, and vaccine manufacturers will be essential to effectively mitigate the risks posed by H5N1. The swift and coordinated response to the detection of H5N1 in US cattle and milk demonstrates a strong commitment to protecting public health and preventing a potential pandemic.
In conclusion, the widespread presence of H5N1 bird flu in US cattle and milk is a significant development that has vaccine scientists and public health officials on high alert. The virus’s ability to infect new species and its potential to mutate and enhance its transmissibility among humans necessitates vigilant monitoring and preparedness. The existing global systems for influenza surveillance and vaccine production provide a robust foundation to respond to any changes in the virus’s behavior, ensuring that public health interventions can be swiftly implemented to mitigate the risk of a potential pandemic.
