Novel Vaccine Platform Aims for Universal Flu Protection
Researchers at Georgia State University's Institute for Biomedical Sciences have developed a novel vaccine platform designed to induce broad, protective immunity against various influenza virus infections. The study, published in ACS Nano, suggests this approach could serve as an effective mucosal vaccine strategy, offering potential for universal influenza vaccine development.
This innovative platform could pave the way for a universal influenza vaccine, providing broad protection against diverse strains.
Vaccine Platform and Mechanism
The developed platform utilizes cell-derived extracellular vesicles (EVs) to display human and avian influenza hemagglutinins (HAs) on their surfaces in an inverted orientation. Hemagglutinin is identified as a primary influenza surface glycoprotein, and extracellular vesicles are natural nanoparticles involved in cell-to-cell communication.
The inverted display aims to present the conserved HA stalk to the immune system. This presentation is intended to induce cross-protective influenza immunity, while simultaneously concealing the highly variable HA head, which is often associated with strain-specific immune responses. According to researchers, influenza viruses have evolved to evade the immune system by concealing conserved structures, making these elements less immunogenic.
Research Methodology and Findings
Investigators evaluated the cellular and mucosal immune responses induced by these multiple HA EV vaccines in mice. The research indicated that EV-based inverted HA vaccines demonstrate potential for developing universal influenza vaccines administered via a mucosal route.
Wandi Zhu, the study's first author, reported that intranasal immunization with the multiple inverted HA-EV vaccine provided complete protection against lethal heterosubtypic challenges involving H7N9 and H5N1 reassortants in mice.
The Role of Mucosal Vaccination
Developing innovative vaccine platforms and delivery strategies capable of inducing protective immunity against diverse influenza virus strains in the respiratory tract is considered crucial for preventing influenza infection and transmission during potential epidemics and pandemics.
Mucosal vaccination is known to induce local immune responses, offering protection against respiratory virus infections at the primary site of invasion. While various mucosal vaccines have undergone study for intranasal administration against respiratory viruses in clinical trials, FluMist is currently the sole FDA-approved mucosal influenza vaccine.
The creation of an effective mucosal vaccination strategy that elicits strong mucosal immune responses with minimal safety concerns remains a continuing need.
Immune Response Profile
Immunization with the multiple HA-EV vaccine was found to elicit a specific immune response profile, including:
- Cross-reactive antibodies targeting influenza HA stalks and viruses.
- Strong virus-specific cellular immune responses.
- A balanced Th1/Th2 immune profile.
Expert Perspectives
Bao-Zhong Wang, a senior author of the study and Distinguished University Professor at Georgia State, shared insights into the platform's efficacy.
"The inverted HA strategy is effective for inducing protective immunity to the conserved HA stalk."
He further stated that cell-origin EVs provide a biocompatible platform for mucosal vaccine delivery and that using EVs to simultaneously display multiple inverted HAs is considered an effective approach for developing universal influenza vaccines.
Funding and Authors
The study received funding from the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH).
Additional authors on the study include Lai Wei, Chunhong Dong, Joo Kyung Kim, Madeline Bruhn, Yao Ma, Alex Ferrante, Arini Arsana, Priscilla Omotara, and Sang-Moo Kang, all from Georgia State's Institute for Biomedical Sciences.