Conformational and Immunogenicity Studies of the Shigella flexneri Serogroup 6 O-Antigen: The Effect of O-Acetylation
| dc.contributor.author | Richardson, Nicole Inge | |
| dc.contributor.author | Ravenscroft, Neil | |
| dc.contributor.author | Arato, Vanessa | |
| dc.contributor.author | Oldrini, Davide | |
| dc.contributor.author | Micoli, Francesca | |
| dc.contributor.author | Kuttel, Michelle M | |
| dc.date.accessioned | 2021-10-12T14:09:10Z | |
| dc.date.available | 2021-10-12T14:09:10Z | |
| dc.date.issued | 2021-04-27 | |
| dc.date.updated | 2021-05-24T15:10:15Z | |
| dc.description.abstract | The pathogenic bacterium <i>Shigella</i> is a leading cause of diarrheal disease and mortality, disproportionately affecting young children in low-income countries. The increasing prevalence of antibiotic resistance in <i>Shigella</i> necessitates an effective vaccine, for which the bacterial lipopolysaccharide O-antigen is the primary target. <i>S. flexneri</i> serotype 6 has been proposed as a multivalent vaccine component to ensure broad protection against <i>Shigella</i>. We have previously explored the conformations of <i>S. flexneri</i> O-antigens from serogroups Y, 2, 3, and 5 that share a common saccharide backbone (serotype Y). Here we consider serogroup 6, which is of particular interest because of an altered backbone repeat unit with non-stoichiometric O-acetylation, the antigenic and immunogenic importance of which have yet to be established. Our simulations show significant conformational changes in serogroup 6 relative to the serotype Y backbone. We further find that O-acetylation has little effect on conformation and hence may not be essential for the antigenicity of serotype 6. This is corroborated by an in vivo study in mice, using Generalized Modules for Membrane Antigens (GMMA) as O-antigen delivery systems, that shows that O-acetylation does not have an impact on the immune response elicited by the <i>S. flexneri</i> serotype 6 O-antigen. | en_US |
| dc.identifier | doi: 10.3390/vaccines9050432 | |
| dc.identifier.apacitation | Richardson, N. I., Ravenscroft, N., Arato, V., Oldrini, D., Micoli, F., & Kuttel, M. M. (2021). Conformational and Immunogenicity Studies of the Shigella flexneri Serogroup 6 O-Antigen: The Effect of O-Acetylation. <i>Vaccines</i>, 9(5), 432. http://hdl.handle.net/11427/35213 | en_ZA |
| dc.identifier.chicagocitation | Richardson, Nicole Inge, Neil Ravenscroft, Vanessa Arato, Davide Oldrini, Francesca Micoli, and Michelle M Kuttel "Conformational and Immunogenicity Studies of the Shigella flexneri Serogroup 6 O-Antigen: The Effect of O-Acetylation." <i>Vaccines</i> 9, 5. (2021): 432. http://hdl.handle.net/11427/35213 | en_ZA |
| dc.identifier.citation | Richardson, N.I., Ravenscroft, N., Arato, V., Oldrini, D., Micoli, F. & Kuttel, M.M. 2021. Conformational and Immunogenicity Studies of the Shigella flexneri Serogroup 6 O-Antigen: The Effect of O-Acetylation. <i>Vaccines.</i> 9(5):432. http://hdl.handle.net/11427/35213 | en_ZA |
| dc.identifier.ris | TY - Journal Article AU - Richardson, Nicole Inge AU - Ravenscroft, Neil AU - Arato, Vanessa AU - Oldrini, Davide AU - Micoli, Francesca AU - Kuttel, Michelle M AB - The pathogenic bacterium <i>Shigella</i> is a leading cause of diarrheal disease and mortality, disproportionately affecting young children in low-income countries. The increasing prevalence of antibiotic resistance in <i>Shigella</i> necessitates an effective vaccine, for which the bacterial lipopolysaccharide O-antigen is the primary target. <i>S. flexneri</i> serotype 6 has been proposed as a multivalent vaccine component to ensure broad protection against <i>Shigella</i>. We have previously explored the conformations of <i>S. flexneri</i> O-antigens from serogroups Y, 2, 3, and 5 that share a common saccharide backbone (serotype Y). Here we consider serogroup 6, which is of particular interest because of an altered backbone repeat unit with non-stoichiometric O-acetylation, the antigenic and immunogenic importance of which have yet to be established. Our simulations show significant conformational changes in serogroup 6 relative to the serotype Y backbone. We further find that O-acetylation has little effect on conformation and hence may not be essential for the antigenicity of serotype 6. This is corroborated by an in vivo study in mice, using Generalized Modules for Membrane Antigens (GMMA) as O-antigen delivery systems, that shows that O-acetylation does not have an impact on the immune response elicited by the <i>S. flexneri</i> serotype 6 O-antigen. DA - 2021-04-27 DB - OpenUCT DP - University of Cape Town IS - 5 J1 - Vaccines LK - https://open.uct.ac.za PY - 2021 T1 - Conformational and Immunogenicity Studies of the Shigella flexneri Serogroup 6 O-Antigen: The Effect of O-Acetylation TI - Conformational and Immunogenicity Studies of the Shigella flexneri Serogroup 6 O-Antigen: The Effect of O-Acetylation UR - http://hdl.handle.net/11427/35213 ER - | en_ZA |
| dc.identifier.uri | http://hdl.handle.net/11427/35213 | |
| dc.identifier.vancouvercitation | Richardson NI, Ravenscroft N, Arato V, Oldrini D, Micoli F, Kuttel MM. Conformational and Immunogenicity Studies of the Shigella flexneri Serogroup 6 O-Antigen: The Effect of O-Acetylation. Vaccines. 2021;9(5):432. http://hdl.handle.net/11427/35213. | en_ZA |
| dc.language.iso | en | en_US |
| dc.publisher.department | Department of Computer Science | en_US |
| dc.publisher.faculty | Faculty of Science | en_US |
| dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_US |
| dc.source | Vaccines | en_US |
| dc.source.journalissue | 5 | en_US |
| dc.source.journalvolume | 9 | en_US |
| dc.source.pagination | 432 | en_US |
| dc.source.uri | https://www.mdpi.com/journal/vaccines | |
| dc.title | Conformational and Immunogenicity Studies of the Shigella flexneri Serogroup 6 O-Antigen: The Effect of O-Acetylation | en_US |
| dc.type | Journal Article | en_US |