Researchers at Georgia State University’s Institute for Biomedical Sciences announced on Apr. 3 that they have developed a novel vaccine platform which induces broad and protective immunity against various influenza virus infections in mice.
This development is significant because it may pave the way for universal influenza vaccines that can be delivered through mucosal routes, potentially improving prevention of infection and transmission during epidemics or pandemics.
The study, published in ACS Nano, used cell-derived extracellular vesicles (EVs) to display human and avian influenza hemagglutinins (HAs) upside-down on their surfaces. This design exposes the conserved HA stalk to the immune system while hiding the highly variable HA head, aiming to produce cross-protective immunity rather than strain-specific responses. The team evaluated immune responses in mice after administering these multiple HA EV vaccines. According to the researchers, EV-based inverted HA vaccines could become a promising approach for developing universal flu vaccines targeting mucosal delivery.
Bao-Zhong Wang, senior author of the study and Distinguished University Professor at Georgia State, said: “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.” The research found that immunization with this vaccine led to cross-reactive antibodies against various influenza strains and robust cellular immune responses.
Wandi Zhu, first author of the study and research assistant professor at Georgia State’s Institute for Biomedical Sciences said: “Intranasal immunization with multiple inverted HA-EV vaccines conferred complete protection against lethal heterosubtypic challenges with H7N9 and H5N1 reassortants.” Other contributors included Lai Wei, Chunhong Dong, Joo Kyung Kim, Madeline Bruhn, Yao Ma, Alex Ferrante, Arini Arsana, Priscilla Omotara and Sang-Moo Kang.
Currently FluMist remains the only FDA-approved mucosal flu vaccine despite ongoing clinical trials exploring other options; therefore an effective strategy like this could address urgent needs in public health by providing strong local immunity with minimized safety concerns.
The work was funded by grants from the National Institute of Allergy and Infectious Diseases at NIH. The full study can be accessed at https://pubs.acs.org/doi/10.1021/acsnano.5c13363.
