Journal Article

Intranasal replicon vaccine establishes mucosal immunity and protects against H5N1 and H7N9 influenza

Mohamath, Raodoh, Beaver, Samuel, McClary, Wynton D., Voigt, Emily A., Kasal, Darshan N., Press, Christopher, Lo, Ethan, Singh, Jasneet, Jennewein, Madeleine F., Cross, Noah, Casper, Corey, Melief, Eduard, Gerhardt, Alana, Reed, Sierra, Brandt, Devin S., Fusco, Pauline, Davis, Michael A., Ykema, Matthew R., Bakken, Julie, Hartwig, Airn Tolnay, Bowen, Richard A.

2026

Overview

Seasonal and pandemic influenza viruses are continuous threats to human health, requiring rapid development of vaccines to multiple evolving viral strains. RNA vaccine technologies have the adaptability and manufacturability to facilitate pandemic preparedness but have limited flexibility in their route of administration, reducing the ability to establish local protective immune responses such as respiratory mucosal immunity. Here, we describe monovalent and bivalent replicon vaccines against A/Vietnam/1203/2004 H5N1 and A/Anhui/PA-1/2013 H7N9. These replicon vaccines express either H5 or H7 hemagglutinin and are formulated with a nanostructured lipid carrier (NLC) that permits both intramuscular (IM) and intranasal (IN) dosing. In mice, IM vaccination established systemic humoral and cellular responses but no detectable mucosal response, while IN administration induced robust systemic and mucosal immunity. The replicon-NLC vaccines protected against morbidity and mortality in ferret challenge models, establishing this intranasally-administered replicon-NLC vaccine platform as a potential pandemic response tool. Vaccines inducing mucosal immunity may provide better protection from respiratory viruses. Here, Ykema et al. demonstrate the utility of a bivalent, mucosally delivered nanostructured lipid carrier-replicon vaccine for induction of mucosal and systemic immunity and protection against morbidity and mortality from H5N1 and H7N9 influenza.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13/1 / 13/21 / 13/31 / 631/250/255/1578 / 631/250/347 / 631/250/590/2293 / 64/60 / Administration, Intranasal / Animals / Antibodies, Viral - immunology / Antigens / Avian flu / Female / Ferrets / Hemagglutinin Glycoproteins, Influenza Virus - genetics / Hemagglutinin Glycoproteins, Influenza Virus - immunology / Hemagglutinins / Humanities and Social Sciences / Humans / Immune response / Immunity / Immunity (Disease) / Immunity, Mucosal - immunology / Influenza / Influenza A Virus, H5N1 Subtype - genetics / Influenza A Virus, H5N1 Subtype - immunology / Influenza A Virus, H7N9 Subtype - genetics / Influenza A Virus, H7N9 Subtype - immunology / Influenza Vaccines - administration & dosage / Influenza Vaccines - immunology / Influenza, Human - immunology / Influenza, Human - prevention & control / Influenza, Human - virology / Injections, Intramuscular / Lipids / Lymphocytes / Manufacturability / Mice / Mice, Inbred BALB C / Morbidity / Mortality / Mucosal immunity / multidisciplinary / Nanostructure / Orthomyxoviridae Infections - immunology / Orthomyxoviridae Infections - prevention & control / Orthomyxoviridae Infections - virology / Pandemics / Replicon - immunology / Science / Science (multidisciplinary) / Statistical analysis / Vaccination / Vaccines / Viral infections