H5N1 avian influenza, commonly known as bird flu, has long ceased to be just a problem for birds. Since its arrival in the United States in 2014, the virus has aggressively expanded its territory, jumping into farm animals and eventually humans.
The situation escalated recently when the virus made a startling leap into dairy cows, catching the scientific community off guard. Since 2022, officials have reported more than 70 human cases in the U.S., including two tragic deaths.
Because the virus continues to circulate widely among animals, it has ongoing chances to adapt. Scientists worry these adaptations could eventually allow H5N1 to spread easily between humans, sparking a new pandemic. But current defense strategies have a flaw. Traditional flu shots are injected into the muscle, building immunity in the blood but leaving the nose — the virus’s main point of entry — vulnerable.
Now, two separate research breakthroughs are looking to close that door. Researchers are developing new intranasal tools — a nasal spray vaccine and an antibody spray — designed to stop the flu exactly where it starts.
Building a Better Wall Against Bird Flu
Current bird flu vaccines rely on older virus strains and are not widely available. To address this, a team at Washington University School of Medicine in St. Louis has developed a vaccine delivered through the nose. It’s as easy to apply as any nasal spray from your local pharmacy.
Published on January 30 in Cell Reports Medicine, the study describes how the researchers’ strategy is preventing infection entirely, rather than just reducing its severity.
“This particular version of bird flu has been around for some time, but the unique and totally unexpected event where it jumped across species into dairy cows in the United States was a clear sign that we should prepare for the event that a pandemic may occur,” said Jacco Boon, PhD, a professor at WashU Medicine.
Boon and his colleagues, including co-authors Michael S. Diamond and David T. Curiel, utilized a technology similar to a COVID-19 nasal vaccine already approved for use in India, which the team had previously helped develop. They inserted a specific protein from H5N1 into a harmless adenovirus. This delivery system carries the vaccine into the body, prompting the immune system to recognize the threat.
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When the team tested this method on hamsters and mice, the nasal vaccine provided near-complete protection against H5N1. While traditional shots offered some defense, the nasal spray triggered a robust immune response in the nasal passages and lungs.
“Our vaccine to the nose and upper airway — not the shot-in-the-arm vaccine people are used to — can protect against upper respiratory infection as well as severe disease,” Boon explained. “This could provide better protection against transmission because it protects against infection in the first place.”
Overcoming the Memory Problem
One of the persistent headaches in flu prevention is the human immune system’s “memory.” Previous bouts of the flu or past vaccinations can sometimes leave a distinct imprint on the immune system, causing it to respond poorly to new vaccines.
The WashU researchers specifically looked for this issue. In their experiments, they found that the new nasal vaccine remained effective even in animals that already possessed immunity from prior flu infections. Nearly every adult human has some history of flu exposure.
“We’ve shown that this nasal vaccine delivery platform we conceived, designed and conducted initial testing on at WashU Medicine can prevent H5N1 infection from taking hold in the nose and lungs,” said Diamond.
“Delivering vaccine directly to the upper airway where you most need protection from respiratory infection could disrupt the cycle of infection and transmission. That’s crucial to slowing the spread of infection for H5N1 as well as other flu strains and respiratory infections.”
The team is now planning further studies in organoids — lab-grown tissues that model human organs — to refine the vaccine further.
The “Liquid Armor” Approach
While the WashU team focuses on teaching the body to fight, another group of scientists is working on a way to lend the body temporary armor.
Researchers from the Harvard T.H. Chan School of Public Health and Leyden Labs have developed a nasal spray containing CR9114, a powerful antibody. Unlike a vaccine, which takes time to train the immune system, antibodies provide immediate protection by neutralizing the virus on contact.
In a study published on February 4 in Science Translational Medicine, this antibody spray showed promise against a wide range of influenza strains. Because CR9114 binds to a part of the virus that rarely changes, it acts as a “universal” shield. In animal tests, it effectively stopped mice and macaques from getting sick when exposed to various flu viruses, including a bird flu strain that infected humans in China in 2013 and a sample from a 1933 flu season.
In preliminary trials with 143 human volunteers, the spray proved safe and well-tolerated. This offers a potential solution for the 646,000 deaths seasonal influenza causes globally each year, filling the gaps left by imperfect seasonal vaccines.
Short-Term Shield for High-Risk Moments
The antibody spray does have limitations compared to a vaccine. The study found that while the spray creates high antibody levels in the nose, those antibodies degrade quickly, within about three hours. To maintain protection, the spray requires twice-daily administration.
Let’s face it, most people won’t comply with such a strict regimen. This logistical hurdle means the spray won’t replace your annual, jab-and-forget flu shot any time soon. However, it could be a critical tool for healthcare workers, immunocompromised people, or during the chaotic early days of a pandemic before a vaccine is ready.
“A major advantage of nasal delivery is that it produces high antibody levels right where the virus enters, using much smaller doses than intravenous antibody treatments. However, the antibody cleared quickly from the nasal surface,” noted immunologist Isabelle Montgomerie from New Zealand’s Malaghan Institute of Medical Research, who was not involved in the study.
“This means it would not replace vaccination, but it could provide short-term protection during a pandemic, especially for high-risk groups,” Montgomerie added.
While the virus can theoretically enter through the mouth, blocking the nasal passage shuts down the primary highway for infection.
“But nonetheless, blocking nasal entry would still intercept the virus at a major access point for infection,” Linda Wakim, from the University of Melbourne, Australia, told New Scientist.
She noted that while the twice-daily dosing makes it less convenient than a jab, “it could be a game changer for specific high-risk groups, such as immunocompromised individuals, frontline healthcare workers, or during a pandemic situation where rapid, short-term population protection is needed while vaccines are being developed or rolled out.”
As H5N1 continues to test the barriers between species, these two technologies represent a shift in how we think about planetary health. We are moving from a reactive stance to a proactive one: standing guard at the very first breath.