Breakthrough Nasal Flu Vaccine Shows Promise in Mice Study

A groundbreaking study published in ACS Nano reveals a promising new approach to influenza vaccination using cell-derived extracellular vesicles (EVs) as a delivery platform. Researchers at Georgia State University have developed a nasal flu vaccine that induces broad, cross-protective immunity against diverse influenza strains in mice.

How the New Vaccine Platform Works

The innovative vaccine strategy involves displaying multiple human and avian influenza hemagglutinins (HAs) in an inverted orientation on the surface of EVs. This design exposes the conserved HA stalk to the immune system while hiding the highly variable HA head, which typically triggers strain-specific immunity.

EVs are natural nanoparticles that facilitate cell-to-cell communication. By presenting the conserved HA stalk, the vaccine aims to induce cross-protective immunity against various influenza strains, potentially leading to a universal flu vaccine.

Study Findings in Mice

The research team evaluated the immune responses induced by the multiple HA EV vaccines in mice. Their findings include:

• Elicitation of cross-reactive antibodies against influenza HA stalks and viruses
• Robust virus-specific cellular immune responses
• A balanced Th1/Th2 immune profile
• Complete protection against lethal challenges with H7N9 and H5N1 reassortant viruses following intranasal immunization

Expert Insights on the Breakthrough

“The influenza virus is smart. They have evolved to evade the immune system by hiding their critical conserved structures, rendering these elements poorly immunogenic. These results highlight that the inverted HA is a smarter strategy for inducing protective immunity to the conserved HA stalk. Meanwhile, cell-origin EVs are a biocompatible platform for mucosal vaccine delivery. Using EVs simultaneously displaying multiple inverted HAs is a powerful approach for developing universal influenza vaccines.”

— Bao-Zhong Wang, senior author and professor at Georgia State University

“Intranasal immunization with multiple inverted HA-EV vaccines conferred complete protection against lethal heterosubtypic challenges with H7N9 and H5N1 reassortants.”

— Wandi Zhu, first author and research assistant professor at Georgia State University

Significance for Future Flu Vaccines

The development of mucosal vaccines is crucial for preventing influenza infection and transmission during potential epidemics and pandemics. Mucosal vaccination induces local immune responses at the site of invasion, offering superior protection against respiratory viruses compared to traditional injectable vaccines.

Currently, FluMist (developed by MedImmune and AstraZeneca) is the only FDA-approved mucosal influenza vaccine. However, creating an effective mucosal vaccination strategy that balances robust immune responses with safety remains an urgent need in public health.

Funding and Research Source

The study was funded by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH). The research was conducted at the Institute for Biomedical Sciences at Georgia State University.

Source: Georgia State University