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

Roux X, Dubuquoy C, Durand G, Tran-Tolla TL, Castagné N, Bernard J, Petit-Camurdan A, Eléouët JF, Riffault S - PLoS ONE (2008)

Bottom Line: These nanoparticles were named sub-nucleocapsid ring structure (N SRS).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.This is the first report of using nanoparticles formed by the recombinant nucleocapsid protein as an efficient and safe intra-nasal vaccine against RSV.

View Article: PubMed Central - PubMed

Affiliation: Unité de Virologie et Immunologie Moléculaires (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 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/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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Related in: MedlinePlus

Nasal vaccination with N SRS induces neutrophil and lymphocyte recruitment in BAL.BALB/c mice were administered i.n. 10 µg N SRS and/or 5 µg LT(R192G) twice at two weeks interval. One group was not immunized. Two weeks after the second immunization, all animals were challenged with 107 PFU hRSV strain A2. Cellular composition of BAL sampled at 0, 5 and 10 days after RSV challenge as determined by May-Grünwald-Giemsa staining: lymphocytes (dotted bars), macrophages (white bars) and neutrophils (grey bars). Results are expressed as mean and SEM percentages from 5–8 individual mice (Data from two experiments with similar results).
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pone-0001766-g004: Nasal vaccination with N SRS induces neutrophil and lymphocyte recruitment in BAL.BALB/c mice were administered i.n. 10 µg N SRS and/or 5 µg LT(R192G) twice at two weeks interval. One group was not immunized. Two weeks after the second immunization, all animals were challenged with 107 PFU hRSV strain A2. Cellular composition of BAL sampled at 0, 5 and 10 days after RSV challenge as determined by May-Grünwald-Giemsa staining: lymphocytes (dotted bars), macrophages (white bars) and neutrophils (grey bars). Results are expressed as mean and SEM percentages from 5–8 individual mice (Data from two experiments with similar results).

Mentions: We also investigated which subsets of cells were recruited in the broncho-alveolar lumen following RSV infection of vaccinated mice. The total number of viable cells recovered from the BAL at 5 days post challenge was markedly enhanced for LT(R192G) and even more for N SRS+LT(R192G) vaccinated mice (Table 1). After cytocentrifugation and May-Grünwald-Giemsa staining of BAL cells collected at days 0, 5 and 10 post RSV challenge (Fig. 4), we observed that 2 administrations of LT(R192G) alone or N SRS+LT(R192G) had increased significantly the percentages of lymphocytes in BAL compared to the control non vaccinated group (Fig. 4 and Table 1). Moreover, virus challenge of mice vaccinated with N SRS+LT(R192G) resulted in an increased percentage of neutrophils in BAL compared to non vaccinated mice or mice treated with LT(R192G) only (Fig. 4 and Table 1). Yet, at no time point was there any significant presence of eosinophils in the BAL of any group.


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

Roux X, Dubuquoy C, Durand G, Tran-Tolla TL, Castagné N, Bernard J, Petit-Camurdan A, Eléouët JF, Riffault S - PLoS ONE (2008)

Nasal vaccination with N SRS induces neutrophil and lymphocyte recruitment in BAL.BALB/c mice were administered i.n. 10 µg N SRS and/or 5 µg LT(R192G) twice at two weeks interval. One group was not immunized. Two weeks after the second immunization, all animals were challenged with 107 PFU hRSV strain A2. Cellular composition of BAL sampled at 0, 5 and 10 days after RSV challenge as determined by May-Grünwald-Giemsa staining: lymphocytes (dotted bars), macrophages (white bars) and neutrophils (grey bars). Results are expressed as mean and SEM percentages from 5–8 individual mice (Data from two experiments with similar results).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2262139&req=5

pone-0001766-g004: Nasal vaccination with N SRS induces neutrophil and lymphocyte recruitment in BAL.BALB/c mice were administered i.n. 10 µg N SRS and/or 5 µg LT(R192G) twice at two weeks interval. One group was not immunized. Two weeks after the second immunization, all animals were challenged with 107 PFU hRSV strain A2. Cellular composition of BAL sampled at 0, 5 and 10 days after RSV challenge as determined by May-Grünwald-Giemsa staining: lymphocytes (dotted bars), macrophages (white bars) and neutrophils (grey bars). Results are expressed as mean and SEM percentages from 5–8 individual mice (Data from two experiments with similar results).
Mentions: We also investigated which subsets of cells were recruited in the broncho-alveolar lumen following RSV infection of vaccinated mice. The total number of viable cells recovered from the BAL at 5 days post challenge was markedly enhanced for LT(R192G) and even more for N SRS+LT(R192G) vaccinated mice (Table 1). After cytocentrifugation and May-Grünwald-Giemsa staining of BAL cells collected at days 0, 5 and 10 post RSV challenge (Fig. 4), we observed that 2 administrations of LT(R192G) alone or N SRS+LT(R192G) had increased significantly the percentages of lymphocytes in BAL compared to the control non vaccinated group (Fig. 4 and Table 1). Moreover, virus challenge of mice vaccinated with N SRS+LT(R192G) resulted in an increased percentage of neutrophils in BAL compared to non vaccinated mice or mice treated with LT(R192G) only (Fig. 4 and Table 1). Yet, at no time point was there any significant presence of eosinophils in the BAL of any group.

Bottom Line: These nanoparticles were named sub-nucleocapsid ring structure (N SRS).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.This is the first report of using nanoparticles formed by the recombinant nucleocapsid protein as an efficient and safe intra-nasal vaccine against RSV.

View Article: PubMed Central - PubMed

Affiliation: Unité de Virologie et Immunologie Moléculaires (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 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/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.

Show MeSH
Related in: MedlinePlus