New Nasal Vaccine Platform Shows Promise for Universal Flu Protection

Researchers at Georgia State University have developed a new vaccine platform designed to provide broad, protective immunity against a wide range of influenza virus infections. The study, published in the journal ACS Nano, demonstrates a strategy to induce cross-protective immunity by targeting conserved parts of the virus.

The platform utilizes cell-derived extracellular vesicles, or EVs, which are natural nanoparticles that facilitate communication between cells. These EVs serve as a delivery system to display various human and avian influenza hemagglutinins (HAs) on their surfaces.

In a departure from traditional vaccine design, the researchers displayed the HAs in an inverted manner. This orientation presents the conserved HA stalk to the immune system to induce broad immunity while hiding the highly variable HA head to avoid immunity that is specific to only one strain.

The influenza virus is smart. They have evolved to evade the immune system by hiding their critical conserved structures, rendering these elements poorly immunogenic,

Bao-Zhong Wang, senior author of the study and professor in the Institute for Biomedical Sciences at Georgia State University

The researchers evaluated the vaccine’s efficacy using mice to measure mucosal and cellular immune responses. The results indicated that the EV-based inverted HA vaccines elicited cross-reactive antibodies against influenza HA stalks and viruses, as well as a balanced Th1/Th2 immune profile.

According to Wandi Zhu, a research assistant professor at Georgia State and the study’s first author, intranasal immunization with multiple inverted HA-EV vaccines conferred complete protection against lethal heterosubtypic challenges with H7N9 and H5N1 reassortants.

The Role of Mucosal Vaccination

The Georgia State University study emphasizes the importance of the mucosal route for respiratory infections. Mucosal vaccination induces local immune responses that protect the respiratory tract at the actual site of viral invasion.

While several mucosal vaccines have undergone clinical trials for intranasal administration, FluMist remains the only FDA-approved mucosal influenza vaccine. Researchers note that a pressing need remains for mucosal strategies that provide robust immune responses while maintaining safety.

Bao-Zhong Wang stated that the use of cell-origin EVs provides a biocompatible platform for this delivery, and using EVs to display multiple inverted HAs is a powerful approach for developing universal influenza vaccines.

Parallel Developments in Universal Vaccines

The effort to create broad-spectrum respiratory protection is also being pursued by other institutions. On February 19, 2026, researchers at Stanford Medicine published a study in the journal Science regarding a different type of universal nasal spray vaccine.

Unlike traditional vaccines that rely on antigen specificity—mimicking a specific component of a pathogen—the Stanford vaccine is designed to supercharge the lungs’ own immune defenses. This keeps the defenses on high alert for several months.

In mouse studies, the Stanford vaccine provided protection against a broad spectrum of respiratory threats, including:

• SARS-CoV-2 and other coronaviruses
• Staphylococcus aureus and Acinetobacter baumannii, which are common hospital-acquired infections
• House dust mites, a common allergen

Bali Pulendran, PhD, the study’s senior author and professor of microbiology and immunology at Stanford Medicine, noted that if such a vaccine is translated to humans, it could potentially replace multiple annual injections for seasonal infections and provide a defense against emerging pandemic viruses.

Both the Georgia State University and Stanford Medicine studies currently rely on mouse models to demonstrate efficacy. These findings represent steps toward the long-term goal of creating universal vaccines that can protect against diverse respiratory viruses and bacteria through a single nasal administration.

The Georgia State University research was funded by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH).