Sub-nucleocapsid nanoparticles: a nasal vaccine against respiratory syncytial virus.
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).


RESULTS
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-gamma-producing CD4(+) T cells.


CONCLUSIONS
This is the first report of using nanoparticles formed by the recombinant nucleocapsid protein as an efficient and safe intra-nasal vaccine against RSV.
Roux
Xavier
X
Unité de Virologie et Immunologie Moléculaires (UR892), INRA, Jouy-en-Josas, France.
Dubuquoy
Catherine
C
Durand
Guillaume
G
Tran-Tolla
Thi-Lan
TL
Castagné
Nathalie
N
Bernard
Julie
J
Petit-Camurdan
Agnès
A
Eléouët
Jean-François
JF
Riffault
Sabine
S
D000281:Administration, Intranasal; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D005434:Flow Cytometry; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D016297:Mutagenesis, Site-Directed; D053758:Nanoparticles; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000276:immunology
D017931:DNA Primers; D014765:Viral Vaccines