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A novel subnucleocapsid nano-platform for mucosal vaccination against influenza targeting the ectodomain of the matrix protein 2

tetano

Editor, Senior Moderator
J Virol. 2013 Oct 23. [Epub ahead of print]
A novel subnucleocapsid nano-platform for mucosal vaccination against influenza targeting the ectodomain of the matrix protein 2.
Herv? PL, Raliou M, Bourdieu C, Dubuquoy C, Petit-Camurdan A, Bertho N, El?ou?t JF, Chevalier C, Riffault S.
Source

INRA, UR0892 Virologie et Immunologie Mol?culaires, 78350 Jouy-en-Josas, France.
Abstract

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 A matrix protein 2 (M2e) is highly conserved and elicit 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, minor weight loss and all survived upon challenge with influenza A/PR8/34 (H1N1) (PR8). We compared the intranasal 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 pre-existing anti-N immunity. Overall, these results show that the N nanoring is a potent carrier for mucosal delivery of vaccinal antigens.

PMID:
24155388
[PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/24155388
 
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