Experimental Flu Vaccine That Protects Against Multiple Strains in Mice

According to a study published by investigators at Georgia State University’s Institute for Biomedical Sciences, a novel vaccine platform has been created to generate broad, protective immunity against multiple influenza virus infections, demonstrating potential as an effective mucosal vaccination approach.

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The study, published in ACS Nano, employed cell-derived extracellular vesicles (EVs) as a vaccine platform to display human and avian influenza hemagglutinins (HAs) in an inverted orientation on the EV surface. This configuration is designed to expose the conserved HA stalk to the immune system, promoting broad, cross-protective immunity, while masking the highly variable HA head to reduce strain-specific responses. 

The scientists used mice to assess cellular and mucosal immune responses triggered by the multiple HA EV vaccines. HA is a primary influenza surface glycoprotein. EVs are naturally occurring nanoparticles that enable cell-to-cell communication.

The researchers determined that EV-based inverted HA vaccines have strong potential to develop universal influenza vaccines that use a mucosal route.

Developing novel vaccine platforms and delivery approaches to generate protective immunity against various influenza virus strains in the respiratory tract is essential for preventing influenza infection and transmission during potential epidemics and pandemics.

By successfully triggering local immune responses, mucosal vaccination guards against respiratory viral infections at the invasion site. The only FDA-approved mucosal influenza vaccine is FluMist (MedImmune and AstraZeneca), despite other mucosal vaccines being investigated for intranasal delivery against respiratory virus infections in research studies.

There is still an urgent need to develop an efficient mucosal vaccination technique that minimizes safety issues while eliciting strong mucosal immune responses.

“The influenza virus is smart. They have evolved to evade the immune system by hiding their critical conserved structures, rendering these elements poorly immunogenic,” said Bao-Zhong Wang.

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, Study Senior Author and Distinguished University Professor, Institute for Biomedical Sciences, Georgia State University

The researchers found that immunization with the multiple HA-EV vaccine produced a balanced Th1/Th2 immunological profile, strong virus-specific cellular immune responses, and cross-reactive antibodies against influenza HA stalks and viruses.

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

Wandi Zhu, Study First Author and Research Assistant Professor, Institute for Biomedical Sciences, Georgia State University