A Novel Subnucleocapsid Nanoplatform for Mucosal Vaccination against Influenza Virus That Targets the Ectodomain of Matrix Protein 2

• Published in: Journal of virology Vol. 88; no. 1; pp. 325 - 338
• Main Authors: Hervé, Pierre-Louis, Raliou, Mariam, Bourdieu, Christiane, Dubuquoy, Catherine, Petit-Camurdan, Agnès, Bertho, Nicolas, Éléouët, Jean-François, Chevalier, Christophe, Riffault, Sabine
• Format: Journal Article
• Language: English
• Published: American Society for Microbiology 2013
• Subjects: Life Sciences
• ISSN: 0022-538X; 1098-5514
• DOI: 10.1128/jvi.01141-13

In this study, subnucleocapsid nanorings formed by the recombinant nucleoprotein (N) of the respiratory syncytial virus were evaluated as a platform to anchor heterologous antigens. The ectodomain of the influenza virus A matrix protein 2 (M2e) is highly conserved and elicits protective antibodies when it is linked to an immunogenic carrier, making it a promising target to develop universal influenza vaccines. In this context, one or three M2e copies were genetically linked to the C terminus of N to produce N-M2e and N-3M2e chimeric recombinant nanorings. Mice were immunized intranasally with N-M2e or N-3M2e or with M2e or 3M2e control peptides. N-3M2e-vaccinated mice showed the strongest mucosal and systemic antibody responses. These mice presented a reduced viral load and minor weight loss, and all survived upon challenge with influenza virus A/PR8/34 (H1N1) (PR8). We compared the intranasal route to the subcutaneous route of N-3M2e immunization. Only the intranasal route induced a strong local IgA response and led to the protection of mice upon challenge. Finally, we demonstrated that the induction of anti-M2e antibodies by N-3M2e is not impaired by preexisting anti-N immunity. Overall, these results show that the N nanoring is a potent carrier for mucosal delivery of vaccinal antigens.