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Removal of the N-Glycosylation Sequon at Position N116 Located in p27 of the Respiratory Syncytial Virus Fusion Protein Elicits Enhanced Antibody Responses after DNA Immunization

Prevention of severe lower respiratory tract infections in infants caused by the human respiratory syncytial virus (hRSV) remains a major public health priority. Currently, the major focus of vaccine development relies on the RSV fusion (F) protein since it is the main target protein for neutralizin...

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Autores principales: Leemans, Annelies, Boeren, Marlies, Van der Gucht, Winke, Pintelon, Isabel, Roose, Kenny, Schepens, Bert, Saelens, Xavier, Bailey, Dalan, Martinet, Wim, Caljon, Guy, Maes, Louis, Cos, Paul, Delputte, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115940/
https://www.ncbi.nlm.nih.gov/pubmed/30110893
http://dx.doi.org/10.3390/v10080426
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author Leemans, Annelies
Boeren, Marlies
Van der Gucht, Winke
Pintelon, Isabel
Roose, Kenny
Schepens, Bert
Saelens, Xavier
Bailey, Dalan
Martinet, Wim
Caljon, Guy
Maes, Louis
Cos, Paul
Delputte, Peter
author_facet Leemans, Annelies
Boeren, Marlies
Van der Gucht, Winke
Pintelon, Isabel
Roose, Kenny
Schepens, Bert
Saelens, Xavier
Bailey, Dalan
Martinet, Wim
Caljon, Guy
Maes, Louis
Cos, Paul
Delputte, Peter
author_sort Leemans, Annelies
collection PubMed
description Prevention of severe lower respiratory tract infections in infants caused by the human respiratory syncytial virus (hRSV) remains a major public health priority. Currently, the major focus of vaccine development relies on the RSV fusion (F) protein since it is the main target protein for neutralizing antibodies induced by natural infection. The protein conserves 5 N-glycosylation sites, two of which are located in the F2 subunit (N27 and N70), one in the F1 subunit (N500) and two in the p27 peptide (N116 and N126). To study the influence of the loss of one or more N-glycosylation sites on RSV F immunogenicity, BALB/c mice were immunized with plasmids encoding RSV F glycomutants. In comparison with F WT DNA immunized mice, higher neutralizing titres were observed following immunization with F N116Q. Moreover, RSV A2-K-line19F challenge of mice that had been immunized with mutant F N116Q DNA was associated with lower RSV RNA levels compared with those in challenged WT F DNA immunized animals. Since p27 is assumed to be post-translationally released after cleavage and thus not present on the mature RSV F protein, it remains to be elucidated how deletion of this glycan can contribute to enhanced antibody responses and protection upon challenge. These findings provide new insights to improve the immunogenicity of RSV F in potential vaccine candidates.
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spelling pubmed-61159402018-08-31 Removal of the N-Glycosylation Sequon at Position N116 Located in p27 of the Respiratory Syncytial Virus Fusion Protein Elicits Enhanced Antibody Responses after DNA Immunization Leemans, Annelies Boeren, Marlies Van der Gucht, Winke Pintelon, Isabel Roose, Kenny Schepens, Bert Saelens, Xavier Bailey, Dalan Martinet, Wim Caljon, Guy Maes, Louis Cos, Paul Delputte, Peter Viruses Article Prevention of severe lower respiratory tract infections in infants caused by the human respiratory syncytial virus (hRSV) remains a major public health priority. Currently, the major focus of vaccine development relies on the RSV fusion (F) protein since it is the main target protein for neutralizing antibodies induced by natural infection. The protein conserves 5 N-glycosylation sites, two of which are located in the F2 subunit (N27 and N70), one in the F1 subunit (N500) and two in the p27 peptide (N116 and N126). To study the influence of the loss of one or more N-glycosylation sites on RSV F immunogenicity, BALB/c mice were immunized with plasmids encoding RSV F glycomutants. In comparison with F WT DNA immunized mice, higher neutralizing titres were observed following immunization with F N116Q. Moreover, RSV A2-K-line19F challenge of mice that had been immunized with mutant F N116Q DNA was associated with lower RSV RNA levels compared with those in challenged WT F DNA immunized animals. Since p27 is assumed to be post-translationally released after cleavage and thus not present on the mature RSV F protein, it remains to be elucidated how deletion of this glycan can contribute to enhanced antibody responses and protection upon challenge. These findings provide new insights to improve the immunogenicity of RSV F in potential vaccine candidates. MDPI 2018-08-14 /pmc/articles/PMC6115940/ /pubmed/30110893 http://dx.doi.org/10.3390/v10080426 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Leemans, Annelies
Boeren, Marlies
Van der Gucht, Winke
Pintelon, Isabel
Roose, Kenny
Schepens, Bert
Saelens, Xavier
Bailey, Dalan
Martinet, Wim
Caljon, Guy
Maes, Louis
Cos, Paul
Delputte, Peter
Removal of the N-Glycosylation Sequon at Position N116 Located in p27 of the Respiratory Syncytial Virus Fusion Protein Elicits Enhanced Antibody Responses after DNA Immunization
title Removal of the N-Glycosylation Sequon at Position N116 Located in p27 of the Respiratory Syncytial Virus Fusion Protein Elicits Enhanced Antibody Responses after DNA Immunization
title_full Removal of the N-Glycosylation Sequon at Position N116 Located in p27 of the Respiratory Syncytial Virus Fusion Protein Elicits Enhanced Antibody Responses after DNA Immunization
title_fullStr Removal of the N-Glycosylation Sequon at Position N116 Located in p27 of the Respiratory Syncytial Virus Fusion Protein Elicits Enhanced Antibody Responses after DNA Immunization
title_full_unstemmed Removal of the N-Glycosylation Sequon at Position N116 Located in p27 of the Respiratory Syncytial Virus Fusion Protein Elicits Enhanced Antibody Responses after DNA Immunization
title_short Removal of the N-Glycosylation Sequon at Position N116 Located in p27 of the Respiratory Syncytial Virus Fusion Protein Elicits Enhanced Antibody Responses after DNA Immunization
title_sort removal of the n-glycosylation sequon at position n116 located in p27 of the respiratory syncytial virus fusion protein elicits enhanced antibody responses after dna immunization
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115940/
https://www.ncbi.nlm.nih.gov/pubmed/30110893
http://dx.doi.org/10.3390/v10080426
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