Nasal Vaccine Shows Promise in Protecting Against H5N1 Bird Flu
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A new intranasal vaccine developed by researchers at Washington University in St. Louis demonstrates strong potential in safeguarding against the highly pathogenic H5N1 avian influenza virus, commonly known as bird flu. The vaccine, tested successfully in animal models, offers a promising new approach to pandemic preparedness as the virus continues to spread globally.
Mounting Threat of H5N1
Since its initial detection in the U.S. in 2014, H5N1 avian influenza has steadily expanded its reach, jumping from wild birds to farm animals and, increasingly, to humans. As of early 2024, the virus has caused over 70 human cases in the U.S. since 2022, tragically resulting in two fatalities. The continued circulation of H5N1 among animal populations raises concerns about its potential to mutate and gain the ability to spread efficiently between humans, potentially triggering another pandemic.
Novel Nasal Vaccine Elicits Strong Immune Response
To address this growing threat, researchers at WashU Medicine engineered an intranasal vaccine designed to stimulate a robust immune response. Testing on hamsters and mice revealed near-complete protection against infection following vaccination. Importantly, the vaccine proved effective even in animals with pre-existing immunity from prior seasonal influenza exposure – a critical advantage over existing vaccine strategies.
“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,” explained a senior researcher involved in the study. “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. This could provide better protection against transmission because it protects against infection in the first place.”
Leveraging Existing Technology for Rapid Response
While a bird flu vaccine currently exists, it’s based on older viral strains and may not be effective against current variants. The WashU Medicine team built upon established nasal vaccine technology previously developed by study co-authors Michael S. Diamond, MD, PhD, and David T. Curiel, MD, PhD. This platform has already demonstrated success with a COVID-19 vaccine available in India since 2022 and recently approved for clinical trials in the U.S.
The team focused on creating an optimal antigen – the component of the virus that triggers an immune response – by selecting specific proteins from currently circulating H5N1 strains. This antigen was then delivered using a harmless, modified adenovirus as a vector, mirroring the approach used in the COVID-19 nasal vaccine.
Superior Protection Compared to Traditional Methods
Animal studies demonstrated that the nasal spray vaccine provided significantly better protection against H5N1 infection than traditional intramuscular immunization. Even low doses of the nasal vaccine offered strong protection against high viral exposure. The nasal delivery method generated a powerful immune response throughout the body, particularly in the nose and respiratory tract.
“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,” stated a co-senior author of the study. “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.”
Addressing Pre-Existing Immunity
A key finding of the research was the vaccine’s effectiveness despite pre-existing immunity from prior influenza exposure. This is a significant advantage, as most individuals have some level of immunity from previous infections or vaccinations, which can sometimes reduce the efficacy of new vaccines. The researchers confirmed that the nasal vaccine maintained strong protection even in individuals with prior flu immunity.
The research team is now planning further studies in animals and human immune tissue models to refine the vaccine and develop versions that minimize the impact of prior seasonal influenza infections and maximize antiviral responses. The findings, published January 30 in Cell Reports Medicine, represent a crucial step forward in preparing for the potential threat of an H5N1 pandemic.
Source: Ying B, Pyles K, Darling TL, Seehra K, Pham T, Huang LC, Harastani HH, Sharma A, Desai P, Kashentseva EA, Curiel DT, Peters B, Case JB, Strauch EM, Diamond MS, Boon ACM. An intranasal adenoviral-vectored vaccine protects against highly pathogenic avian influenza H5N1 in naïve and antigen-experienced animals. Cell Reports Medicine. https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(25)00655-X
