sub-nucleocapsid nanoparticles a nasal vaccine against respiratory syncytial virussub-nucleocapsid纳米粒子鼻抗呼吸道合胞病毒的疫苗.pdf

Sub-Nucleocapsid Nanoparticles: A Nasal Vaccine against Respiratory Syncytial Virus ´ Xavier Roux, Catherine Dubuquoy, Guillaume Durand, Thi-Lan Tran-Tolla, Nathalie Castagne, Julie ` ´ ¨ Bernard, Agnes Petit-Camurdan, Jean-Franc¸ois Eleouet, Sabine Riffault* ´ ´ Unite de Virologie et Immunologie Moleculaires (UR892), INRA, Jouy-en-Josas, France Abstract 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 immuniza