Early-stage clinical trial demonstrates promise of intranasal influenza vaccine in generating broad immunity

BALTIMORE, MD., November 6, 2025--Researchers at the University of Maryland School of Medicine’s Center for Vaccine Development and Global Health (CVD) reported encouraging results from an early phase clinical trial that found an experimental intranasal vaccine triggered a broad immune response against multiple strains of H5N1 “bird flu”. The study, published today in the journal Nature Communications, highlights the potential of mucosal immunization strategies--where vaccines are squirted into the nostrils--to prime immune defenses against diverse influenza strains.

The spread of H5N1 influenza in animals with spillover into human populations globally highlights the critical need for effective countermeasures to protect our communities from this and other pathogens with pandemic potential,” said study corresponding author Justin Ortiz, MD, MS, Professor of Medicine at the University of Maryland School of Medicine (UMSOM) and vaccine researcher at CVD. “This trial shows that this intranasal, shelf-stable H5N1 vaccine could play a major role in pandemic preparedness, offering a practical and scalable way to help protect people from evolving strains of the virus.”

Current influenza vaccines, administered intramuscularly, primarily induce systemic immune responses that protect against symptomatic illness when well-matched to circulating strains. However, these vaccines may be less effective at preventing the spread of infection from one person to another. Mucosal vaccines, delivered intranasally, aim to stimulate immunity at the site of infection, offering a promising approach to reduce transmission.

In this randomized, controlled trial, 40 healthy adult volunteers were randomly assigned to receive different doses of an H5 flu vaccine with BlueWillow’s NanoVax® W₈₀5EC adjuvant. Control groups received a placebo or a high-dose of the H5 vaccine without the adjuvant. Six months later, all volunteers received an intramuscular H5 flu booster.

The NanoVax H5 intranasal vaccine was found to be safe and well tolerated. Importantly, only people who received the boosted nasal vaccine showed strong immune “priming”—meaning their immune systems were activated and ready to respond—as revealed later, when they were given a single dose of an intramuscular H5 flu shot. Even on its own without a booster, the NanoVax H5 intranasal vaccine triggered mucosal and systemic immune defenses —something other intranasal recombinant H5 flu vaccines have not achieved in clinical trials.

“The vaccine also helped the immune system recognize multiple versions of the H5N1 virus, which is key because there are different versions of the virus and they change over time,” said study co-lead author Meagan E. Deming, MD, PhD, Assistant Professor of Medicine at UMSOM. “The use of the adjuvant also suggests this approach might allow for lower doses of the vaccine, which could make our current vaccine stocks available to more people in the event of an outbreak.”

Specifically, the study found that volunteers who received the adjuvanted H5 vaccine had strong immune activity including higher levels of protective antibodies (IgG and IgA), more memory immune cells, and better ability to kill infected cells.

“These findings demonstrate successful mucosal priming and the potential for broad cross-clade immunity,” said study co-lead author Franklin R. Toapanta, MD, PhD, Associate Professor of Medicine at UMSOM.  “The intranasal vaccine’s ability to elicit mucosal and cellular immune responses, coupled with strong antibody-dependent cell cytotoxicity, underscores its promise as part of next-generation influenza prevention strategies.”

The study was funded by a grant from the National Institutes of Allergy and Infectious Diseases (U01AI148081).

"The research aligns with global public health priorities to develop vaccines that reduce transmission and provide broader protection against emerging influenza strains," said Mark T. Gladwin, MD, Dean of the University of Maryland School of Medicine, Vice President for Medical Affairs, University of Maryland, Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor. "It also highlights the need for further research into mucosal immune biomarkers and alternative immune correlates of protection, which may accelerate development of intranasal influenza vaccines."

About the University of Maryland School of Medicine

The University of Maryland School of Medicine, established in 1807 as the first public medical school in the U.S., continues today as one of the fastest growing, top-tier biomedical research enterprises in the world.  The School has nearly $500 million total research funding, 46 departments, centers, and institutes, more than 2,200 student trainees and over 3,000 faculty members, including notable members of the National Academy of Medicine.  As the largest public medical school in the DC/MD/VA region, faculty-physicians are working to help patients manage chronic diseases like obesity, cancer, heart disease and addiction, while also working on cutting-edge research to address the most critical generational health challenges. In 2024, the School ranked #12 among public medical schools and #27 among all medical schools for R&D expenditures by the National Science Foundation. With a $1.3 billion total operating budget, the School partners with the University of Maryland Medical Center to serve nearly 2 million patients annually. The School's global reach extends around the world with research and treatment facilities in 33 countries. In Maryland, the School of Medicine is spearheading new initiatives in AI and health computing and partnering with the University of Maryland BioPark to develop new medical technologies and bioengineering ventures. For more information, visit medschool.umaryland.edu.

About the Center for Vaccine Development and Global Health

For over 40 years, researchers in the Center for Vaccine Development and Global Health (CVD) have worked domestically and internationally to develop, test, and deploy vaccines to aid the world's underserved populations. CVD is an academic enterprise engaged in the full range of infectious disease interventions, from basic laboratory research through vaccine development, pre-clinical and clinical evaluation, large-scale pre-licensure field studies, and post-licensure assessments. CVD has created and tested vaccines against cholera, typhoid fever, paratyphoid

fever, non-typhoidal Salmonella disease, shigellosis (bacillary dysentery), Escherichia coli diarrhea, nosocomial pathogens, tularemia, influenza, coronaviruses, malaria, dengue, ebola, and other infectious diseases. CVD's research covers the broader goal of improving global health by conducting innovative, leading research in Baltimore and around the world. Our researchers are developing new and improved ways to diagnose, prevent, treat, control, and eliminate diseases of global impact, including COVID-19. In addition, CVD's work focuses on the ever-growing challenge of antimicrobial resistance.