Neonatal Nasal Vaccination with the Nucleoprotein of the Respiratory Syncytial Virus Elicits Virus-protective but Airway-pathogenic Th2-biased Immunity that can be Modulated by the Choice of Adjuvants
Résumé
There is still no licensed vaccine against human respiratory syncytial virus (RSV) which causes severe bronchiolitis in yound children. The nucleoprotein N, a major component of the RSV nucleocapsid, is remarkably conserved among RSV subtypes and is recognized as a target of protective T cell responses. We reported a method to produce recombinant N assembling in homogenous rings composed of 10-11 N subunits.Intranasal vaccination of adult BALB/c mice with N-rings and detoxified E.coli enterotoxin LT(R192G) as adjuvant (provided by J. Clements, USA), proved protective against an RSV challenge, without causing significant lung inflammatory reactions. In the present study, we evaluated the vaccine potential of N-rings in 5 to 7 day-old BALB/c pups: a single intranasal administration of N-rings with LT(R192G) provided a significant reduction of the viral load after an RSV challenge at five weeks of age. However, neonatal vaccination also generated an enhanced lung infiltration by eosinophils following the RSV challenge. Analysis of antibody subclasses and cytokines produced after an RSV challenge or a boost administration of the vaccine suggested that neonatal vaccination induced a long lasting Th2 biased local immune memory. This early Th2 bias could be prevented by adding CpG-ODN to the vaccine formulation, but then the protection against virus replication was also reduced. In conclusion, protective vaccination against RSV can be achieve in neonates but requires an appropriate combinations of adjuvant.
Domaines
Pneumologie et système respiratoireOrigine | Fichiers éditeurs autorisés sur une archive ouverte |
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