Promising Early Results for Intranasal Flu Vaccine Against H5N1

Researchers at the University of Maryland School of Medicine have reported promising findings from an early-phase clinical trial of an experimental intranasal vaccine targeting the H5N1 strain of avian influenza. The study, detailed in the journal Nature Communications, suggests that this innovative mucosal vaccine may effectively generate a broad immune response against multiple strains of the virus, which has raised concerns due to its potential for human infection.

This randomized, controlled trial involved 40 healthy adult volunteers who received varying doses of the H5 flu vaccine, which utilized BlueWillow’s NanoVax W 80 5EC adjuvant. Participants in control groups received either a placebo or a high-dose version of the vaccine without the adjuvant. Six months post-vaccination, all volunteers received an intramuscular booster of the H5 flu vaccine.

The results indicated that the NanoVax H5 intranasal vaccine was both safe and well tolerated. Notably, only those who received the intranasal vaccine demonstrated effective immune “priming,” preparing their immune systems for a subsequent intramuscular booster. The study revealed that even when administered alone, the intranasal vaccine activated both mucosal and systemic immune defenses—a significant advancement over previous intranasal recombinant H5 flu vaccines that failed to achieve similar outcomes.

Justin Ortiz, MD, MS, lead author of the study, emphasized the urgency of developing effective vaccines against H5N1, stating, “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.” He noted that this intranasal vaccine could play a significant role in pandemic preparedness.

The study also found that the vaccine enabled the immune system to recognize various versions of the H5N1 virus, an essential factor given the virus’s ability to mutate over time. Meagan E. Deming, MD, Ph.D., co-lead author, pointed out the potential for using the adjuvant to lower vaccine doses, which could increase vaccine availability during outbreaks.

In terms of immune response, participants who received the adjuvanted H5 vaccine exhibited robust immune activity. This included elevated levels of protective antibodies, enhanced memory immune cells, and improved capacity to eliminate infected cells. Franklin R. Toapanta, MD, Ph.D., another co-lead author, stated, “These findings demonstrate successful mucosal priming and the potential for broad cross-clade immunity.”

The research aligns with global public health initiatives aimed at developing vaccines that not only reduce transmission but also provide broader protection against emerging influenza strains. Mark T. Gladwin, MD, Dean of the University of Maryland School of Medicine, highlighted the importance of continued research into mucosal immune biomarkers and alternative immune correlates of protection, which could expedite the development of intranasal influenza vaccines.

As the world grapples with the ongoing threat of influenza viruses, this study underscores the importance of innovative vaccination strategies. The development of effective intranasal vaccines could significantly enhance public health responses to future influenza outbreaks and potential pandemics.

For additional details, refer to the study titled, “An Intranasal Adjuvanted, Recombinant Influenza A/H5 Vaccine Primes Against Diverse H5N1 Clades: A Phase I Trial,” published in Nature Communications, 2025. DOI: 10.1038/s41467-025-64686-3.