Researchers develop nasal spray H5N1 avian influenza vaccine
Generation and characterization of DelNS1-H5N1 vaccines. Credit: Nature Communications (2025). DOI: 10.1038/s41467-025-58504-z
The State Key Laboratory for Emerging Infectious Diseases at the University of Hong Kong (HKU) and the InnoHK Center for Virology, Vaccinology and Therapeutics (CVVT) have pioneered an influenza virus vector-based nasal spray vaccine platform and developed a nasal spray H5N1 avian influenza vaccine. The study is published in Nature Communications.
During the early COVID-19 pandemic, this platform enabled the rapid development of a nasal spray vaccine in collaboration with mainland China's Wantai BioPharm. After completing Phase 1–3 clinical trials, it was approved in 2022 as the world's first nasal spray COVID-19 vaccine.
The world has just emerged from the COVID-19 pandemic, with vivid memories of the devastating impacts of the SARS-CoV-2 virus on human health, economies, and social stability in recent years. Although SARS-CoV-2 has gradually evolved into a seasonal respiratory virus, new pandemics are inevitable. The World Health Organization (WHO) and many nations have already begun preparations to address potential future pandemics caused by "Disease X."
The H5N1 avian influenza virus, first detected in humans in Hong Kong in 1997, has spread globally, spawning multiple variants and causing cross-species infections. It is now a top candidate for triggering a human pandemic. Since early 2024, uncontrolled outbreaks in U.S. dairy farms have led to dozens of human infections, with the virus circulating in cattle and other animals.
Genetic surveillance has identified mutations that enhance H5N1's affinity for human upper respiratory cells, raising concerns that further adaptation or recombination with seasonal flu could significantly increase the risk of a pandemic. Preparation for a potential H5N1 pandemic is urgent, with the U.S. allocating 500 million USD to pharmaceutical companies for mRNA-based vaccine development.
Lessons from the COVID-19 pandemic underscore that safe, effective, and rapidly deployable vaccines are the most critical strategy for pandemic response. Current vaccines, including mRNA vaccines, effectively prevent severe disease and reduce mortality but fail to curb viral transmission. This limitation stems from intramuscular administration, which induces strong systemic antibodies but insufficient immunity in the upper respiratory tract.
Most vaccines also require multiple doses for efficacy. A nasal spray vaccine offering single-dose protection could play a pivotal role in outbreak control by rapidly inducing mucosal immunity at the primary site of viral entry.
To address the emerging H5N1 threat, the HKU and CVVT team used the influenza virus vector-based nasal spray vaccine platform to develop a nasal spray H5N1 avian influenza vaccine. Animal studies confirm its high safety profile and ability to induce comprehensive immunity, including neutralizing antibodies, T-cell responses, and mucosal immunity in the upper respiratory tract.
Crucially, a single dose provides robust protection against infection and sustains immune memory. Further clinical trials could position this vaccine as a critical reserve for future H5N1 outbreaks, drastically shortening deployment timelines. Its nasal delivery mechanism also promises to curb viral transmission early in an outbreak.
More information: Ying Liu et al, Intranasal influenza virus-vectored vaccine offers protection against clade 2.3.4.4b H5N1 infection in small animal models, Nature Communications (2025). DOI: 10.1038/s41467-025-58504-z
Provided by The University of Hong Kong