Sub-nucleocapsid nanoparticles: a nasal vaccine against respiratory syncytial virus
2008
Roux , Xavier (INRA , Jouy-En-Josas (France). UR 0892 Unité de recherche Virologie et Immunologie Moléculaires) | Dubuquoy , Catherine (INRA , Jouy-En-Josas (France). UR 0892 Unité de recherche Virologie et Immunologie Moléculaires) | Durand , Guillaume (INRA , Jouy-En-Josas (France). UR 0892 Unité de recherche Virologie et Immunologie Moléculaires) | Tran-Tolla , Thi-Lan (INRA , Jouy-En-Josas (France). UR 0892 Unité de recherche Virologie et Immunologie Moléculaires) | Castagné , Nathalie (INRA , Jouy-En-Josas (France). UR 0892 Unité de recherche Virologie et Immunologie Moléculaires) | Bernard , Julie (INRA , Jouy-En-Josas (France). UR 0892 Unité de recherche Virologie et Immunologie Moléculaires) | Petit Camurdan , Agnes (INRA , Jouy-En-Josas (France). UR 0892 Unité de recherche Virologie et Immunologie Moléculaires) | Eleouet , Jean Francois (INRA , Jouy-En-Josas (France). UR 0892 Unité de recherche Virologie et Immunologie Moléculaires) | Riffault , Sabine (INRA , Jouy-En-Josas (France). UR 0892 Unité de recherche Virologie et Immunologie Moléculaires)
Background: Bronchiolitis caused by the respiratory syncytial virus (RSV) in infants less than two years old is a growing public health concern worldwide, and there is currently no safe and effective vaccine. A major component of RSV nucleocapsid, the nucleoprotein (N), has been so far poorly explored as a potential vaccine antigen, even though it is a target of protective anti-viral T cell responses and is remarkably conserved between human RSV A and B serotypes. We recently reported a method to produce recombinant N assembling in homogenous rings composed of 10–11 N subunits enclosing a bacterial RNA. These nanoparticles were named sub-nucleocapsid ring structure (N SRS). Methodology and Principal Findings: The vaccine potential of N SRS was evaluated in a well-characterized and widely acknowledged mouse model of RSV infection. BALB/c adult mice were immunized intranasally with N SRS adjuvanted with the detoxified E. coli enterotoxin LT(R192G). Upon RSV challenge, vaccinated mice were largely protected against virus replication in the lungs, with a mild inflammatory lymphocytic and neutrophilic reaction in their airways. Mucosal immunization with N SRS elicited strong local and systemic immunity characterized by high titers of IgG1, IgG2a and IgA anti-N antibodies, antigen-specific CD8+ T cells and IFN-c-producing CD4+ T cells. Conclusions/Significance: This is the first report of using nanoparticles formed by the recombinant nucleocapsid protein as an efficient and safe intra-nasal vaccine against RSV.
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