Researchers report a promising vaccine platform in a study published in ACS Nano that may offer broad protection against diverse influenza viruses. The approach uses cell-derived extracellular vesicles (EVs) that display inverted forms of influenza hemagglutinins (HAs) on their surface, with the aim of developing a mucosal vaccine to protect the respiratory tract and limit transmission in epidemics or pandemics.
In the inverted arrangement the HA stalk is more exposed to the immune system while the highly variable HA head is less visible. Because the stalk contains conserved structures shared across many strains, focusing the immune response on the stalk can induce cross-reactive protection. EVs are natural nanoparticles that mediate cell communication and can serve as a biocompatible delivery platform for such vaccines.
The investigators evaluated multiple HA-EV vaccines in mice and measured both cellular and mucosal immune responses. Immunization elicited cross-reactive antibodies against HA stalks and viruses, robust virus-specific cellular immunity and a balanced Th1/Th2 profile. Importantly, intranasal immunization with multiple inverted HA-EV vaccines conferred complete protection against lethal heterosubtypic challenges with H7N9 and H5N1 reassortants. The authors conclude that inverted HA on EVs is a powerful strategy for developing universal influenza vaccines. The work was funded by NIAID of the NIH and reported by Georgia State University.
Difficult words
- extracellular vesicle — Small particles released by cells for communicationextracellular vesicles
- hemagglutinin — Viral surface protein of influenza involved in entryhemagglutinins
- inverted — Placed in the opposite or reversed orientation
- mucosal — Relating to the moist lining of respiratory tractmucosal vaccine
- conserved — Remaining similar across different virus strainsconserved structures
- cross-reactive — Reacting against related strains or similar antigenscross-reactive antibodies
- intranasal — Delivered through the nose into respiratory passagesintranasal immunization
- reassortant — Virus formed by mixing gene segments from strainsreassortants
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Discussion questions
- What are the advantages of focusing an immune response on the HA stalk rather than the HA head? Give two reasons based on the article.
- What practical benefits might a mucosal (intranasal) vaccine have for controlling epidemics or pandemics?
- What challenges or safety questions would you want researchers to address before using EV-based inverted HA vaccines in people?
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