Nucleoprotein nanostructures combined with adjuvants adapted to the neonatal immune context: a candidate mucosal RSV vaccine.

<h4>Background</h4>The human respiratory syncytial virus (hRSV) is the leading cause of severe bronchiolitis in infants worldwide. The most severe RSV diseases occur between 2 and 6 months-of-age, so pediatric vaccination will have to be started within the first weeks after birth, when t...

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Autores principales: Aude Remot, Xavier Roux, Catherine Dubuquoy, Jenna Fix, Stephan Bouet, Mohammed Moudjou, Jean-François Eléouët, Sabine Riffault, Agnès Petit-Camurdan
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Publicado: Public Library of Science (PLoS) 2012
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Acceso en línea:https://doaj.org/article/e8b59c5f1336419d9c4e58df6e4c0a5b
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spelling oai:doaj.org-article:e8b59c5f1336419d9c4e58df6e4c0a5b2021-11-18T07:17:31ZNucleoprotein nanostructures combined with adjuvants adapted to the neonatal immune context: a candidate mucosal RSV vaccine.1932-620310.1371/journal.pone.0037722https://doaj.org/article/e8b59c5f1336419d9c4e58df6e4c0a5b2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22655066/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>The human respiratory syncytial virus (hRSV) is the leading cause of severe bronchiolitis in infants worldwide. The most severe RSV diseases occur between 2 and 6 months-of-age, so pediatric vaccination will have to be started within the first weeks after birth, when the immune system is prone to Th2 responses that may turn deleterious upon exposure to the virus. So far, the high risk to prime for immunopathological responses in infants has hampered the development of vaccine. In the present study we investigated the safety and efficacy of ring-nanostructures formed by the recombinant nucleoprotein N of hRSV (N(SRS)) as a mucosal vaccine candidate against RSV in BALB/c neonates, which are highly sensitive to immunopathological Th2 imprinting.<h4>Methodology and principal findings</h4>A single intranasal administration of N(SRS) with detoxified E. coli enterotoxin LT(R192G) to 5-7 day old neonates 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 neutrophils and 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 Th2 biased local immune memory. This Th2 bias and the eosinophilic reaction could be prevented by adding CpG to the vaccine formulation, which, however did not prevent pulmonary inflammation and neutrophil infiltration upon viral challenge.<h4>Conclusions/significance</h4>In conclusion, protective vaccination against RSV can be achieved in neonates but requires an appropriate combination of adjuvants to prevent harmful Th2 imprinting.Aude RemotXavier RouxCatherine DubuquoyJenna FixStephan BouetMohammed MoudjouJean-François EléouëtSabine RiffaultAgnès Petit-CamurdanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 5, p e37722 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Aude Remot
Xavier Roux
Catherine Dubuquoy
Jenna Fix
Stephan Bouet
Mohammed Moudjou
Jean-François Eléouët
Sabine Riffault
Agnès Petit-Camurdan
Nucleoprotein nanostructures combined with adjuvants adapted to the neonatal immune context: a candidate mucosal RSV vaccine.
description <h4>Background</h4>The human respiratory syncytial virus (hRSV) is the leading cause of severe bronchiolitis in infants worldwide. The most severe RSV diseases occur between 2 and 6 months-of-age, so pediatric vaccination will have to be started within the first weeks after birth, when the immune system is prone to Th2 responses that may turn deleterious upon exposure to the virus. So far, the high risk to prime for immunopathological responses in infants has hampered the development of vaccine. In the present study we investigated the safety and efficacy of ring-nanostructures formed by the recombinant nucleoprotein N of hRSV (N(SRS)) as a mucosal vaccine candidate against RSV in BALB/c neonates, which are highly sensitive to immunopathological Th2 imprinting.<h4>Methodology and principal findings</h4>A single intranasal administration of N(SRS) with detoxified E. coli enterotoxin LT(R192G) to 5-7 day old neonates 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 neutrophils and 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 Th2 biased local immune memory. This Th2 bias and the eosinophilic reaction could be prevented by adding CpG to the vaccine formulation, which, however did not prevent pulmonary inflammation and neutrophil infiltration upon viral challenge.<h4>Conclusions/significance</h4>In conclusion, protective vaccination against RSV can be achieved in neonates but requires an appropriate combination of adjuvants to prevent harmful Th2 imprinting.
format article
author Aude Remot
Xavier Roux
Catherine Dubuquoy
Jenna Fix
Stephan Bouet
Mohammed Moudjou
Jean-François Eléouët
Sabine Riffault
Agnès Petit-Camurdan
author_facet Aude Remot
Xavier Roux
Catherine Dubuquoy
Jenna Fix
Stephan Bouet
Mohammed Moudjou
Jean-François Eléouët
Sabine Riffault
Agnès Petit-Camurdan
author_sort Aude Remot
title Nucleoprotein nanostructures combined with adjuvants adapted to the neonatal immune context: a candidate mucosal RSV vaccine.
title_short Nucleoprotein nanostructures combined with adjuvants adapted to the neonatal immune context: a candidate mucosal RSV vaccine.
title_full Nucleoprotein nanostructures combined with adjuvants adapted to the neonatal immune context: a candidate mucosal RSV vaccine.
title_fullStr Nucleoprotein nanostructures combined with adjuvants adapted to the neonatal immune context: a candidate mucosal RSV vaccine.
title_full_unstemmed Nucleoprotein nanostructures combined with adjuvants adapted to the neonatal immune context: a candidate mucosal RSV vaccine.
title_sort nucleoprotein nanostructures combined with adjuvants adapted to the neonatal immune context: a candidate mucosal rsv vaccine.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/e8b59c5f1336419d9c4e58df6e4c0a5b
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