Evaluating the Impact of N-Glycan Sequon Removal in the p27 Peptide on RSV F Protein Immunogenicity and Functionality
Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections in young children, elderly and immunocompromised patients worldwide. The RSV fusion (F) protein, which has 5–6 N-glycosylation sites depending on the strain, is a major target for vaccine development....
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MDPI AG
2024-11-01
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| Series: | Viruses |
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| author | Lotte Jacobs Annelies Leemans Kim Stobbelaar Axelle Fransen Paul Cos Peter Delputte |
| author_facet | Lotte Jacobs Annelies Leemans Kim Stobbelaar Axelle Fransen Paul Cos Peter Delputte |
| author_sort | Lotte Jacobs |
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| description | Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections in young children, elderly and immunocompromised patients worldwide. The RSV fusion (F) protein, which has 5–6 N-glycosylation sites depending on the strain, is a major target for vaccine development. Two to three of these sites are located in the p27 peptide, which is considered absent in virions. Prior research from our group showed that removing the N-glycan at position 116 (N116) in p27 led to higher neutralizing antibody responses and better protection against RSV. In this study, the effect of single, double and triple N-glycan deletion mutations in F p27 was evaluated. Surprisingly, all mutants exhibited similar expressions and functionality to the wild-type F protein. All F p27 glycomutants induced neutralizing antibodies and lowered lung viral loads after an RSV challenge in a mouse model. Although N-glycans in p27 influence immune responses, their exact role in RSV biology remains unclear. Possibly, these glycans, which are mostly conserved, play a role in other aspects of virus replication and biology. |
| format | Article |
| id | doaj-art-4f40d0104e224e539c9b0286b48db2ee |
| institution | Kabale University |
| issn | 1999-4915 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj-art-4f40d0104e224e539c9b0286b48db2ee2024-12-27T14:59:01ZengMDPI AGViruses1999-49152024-11-011612184810.3390/v16121848Evaluating the Impact of N-Glycan Sequon Removal in the p27 Peptide on RSV F Protein Immunogenicity and FunctionalityLotte Jacobs0Annelies Leemans1Kim Stobbelaar2Axelle Fransen3Paul Cos4Peter Delputte5Laboratory for Microbiology, Parasitology and Hygiene, Infla-Med Centre of Excellence, University of Antwerp (UA), Universiteitsplein 1 S.7, 2610 Antwerp, BelgiumLaboratory for Microbiology, Parasitology and Hygiene, Infla-Med Centre of Excellence, University of Antwerp (UA), Universiteitsplein 1 S.7, 2610 Antwerp, BelgiumLaboratory for Microbiology, Parasitology and Hygiene, Infla-Med Centre of Excellence, University of Antwerp (UA), Universiteitsplein 1 S.7, 2610 Antwerp, BelgiumLaboratory for Microbiology, Parasitology and Hygiene, Infla-Med Centre of Excellence, University of Antwerp (UA), Universiteitsplein 1 S.7, 2610 Antwerp, BelgiumLaboratory for Microbiology, Parasitology and Hygiene, Infla-Med Centre of Excellence, University of Antwerp (UA), Universiteitsplein 1 S.7, 2610 Antwerp, BelgiumLaboratory for Microbiology, Parasitology and Hygiene, Infla-Med Centre of Excellence, University of Antwerp (UA), Universiteitsplein 1 S.7, 2610 Antwerp, BelgiumRespiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections in young children, elderly and immunocompromised patients worldwide. The RSV fusion (F) protein, which has 5–6 N-glycosylation sites depending on the strain, is a major target for vaccine development. Two to three of these sites are located in the p27 peptide, which is considered absent in virions. Prior research from our group showed that removing the N-glycan at position 116 (N116) in p27 led to higher neutralizing antibody responses and better protection against RSV. In this study, the effect of single, double and triple N-glycan deletion mutations in F p27 was evaluated. Surprisingly, all mutants exhibited similar expressions and functionality to the wild-type F protein. All F p27 glycomutants induced neutralizing antibodies and lowered lung viral loads after an RSV challenge in a mouse model. Although N-glycans in p27 influence immune responses, their exact role in RSV biology remains unclear. Possibly, these glycans, which are mostly conserved, play a role in other aspects of virus replication and biology.https://www.mdpi.com/1999-4915/16/12/1848RSVfusion proteinp27 peptideN-glycosylationDNA immunization |
| spellingShingle | Lotte Jacobs Annelies Leemans Kim Stobbelaar Axelle Fransen Paul Cos Peter Delputte Evaluating the Impact of N-Glycan Sequon Removal in the p27 Peptide on RSV F Protein Immunogenicity and Functionality Viruses RSV fusion protein p27 peptide N-glycosylation DNA immunization |
| title | Evaluating the Impact of N-Glycan Sequon Removal in the p27 Peptide on RSV F Protein Immunogenicity and Functionality |
| title_full | Evaluating the Impact of N-Glycan Sequon Removal in the p27 Peptide on RSV F Protein Immunogenicity and Functionality |
| title_fullStr | Evaluating the Impact of N-Glycan Sequon Removal in the p27 Peptide on RSV F Protein Immunogenicity and Functionality |
| title_full_unstemmed | Evaluating the Impact of N-Glycan Sequon Removal in the p27 Peptide on RSV F Protein Immunogenicity and Functionality |
| title_short | Evaluating the Impact of N-Glycan Sequon Removal in the p27 Peptide on RSV F Protein Immunogenicity and Functionality |
| title_sort | evaluating the impact of n glycan sequon removal in the p27 peptide on rsv f protein immunogenicity and functionality |
| topic | RSV fusion protein p27 peptide N-glycosylation DNA immunization |
| url | https://www.mdpi.com/1999-4915/16/12/1848 |
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