Molecular Modeling of the Shigella flexneri Serogroup 3 and 5 O-Antigens and Conformational Relationships for a Vaccine Containing Serotypes 2a and 3a
| dc.contributor.author | Hlozek, Jason | |
| dc.contributor.author | Owen, Sara | |
| dc.contributor.author | Ravenscroft, Neil | |
| dc.contributor.author | Kuttel, Michelle M. | |
| dc.date.accessioned | 2021-10-13T11:48:56Z | |
| dc.date.available | 2021-10-13T11:48:56Z | |
| dc.date.issued | 2020-11-02 | |
| dc.date.updated | 2020-12-24T18:15:19Z | |
| dc.description.abstract | The pathogenic bacterium Shigella flexneri is a leading global cause of diarrheal disease. The O-antigen is the primary vaccine target and distinguishes the 30 serotypes reported. Except for serotype 6, all S. flexneri serotypes have a common backbone repeating unit (serotype Y), with variations in substitution creating the various serotypes. A quadrivalent vaccine containing serotypes 2a and 3a (as well as 6 and Shigella sonnei) is proposed to provide broad protection against non-vaccine S. flexneri serotypes through shared epitopes and conformations. Here we model the O-antigen (O-Ag) conformations of serogroups 3 and 5: a continuation of our ongoing systematic study of the S. flexneri O-antigens that began with serogroup 2. Our simulations show that S. flexneri serogroups 2, 3, and 5 all have flexible O-Ags, with substitutions of the backbone altering the chain conformations in different ways. Our analysis suggests three general heuristics for the effects of substitution on the Shigella O-Ag conformations: (1) substitution on rhamnose C reduces the extension of the O-Ag chain; (2) substitution at O-3 of rhamnose A restricts the O-Ags to predominantly helical conformations, (3) substitution at O-3 of rhamnose B has only a slight effect on conformation. The common O-Ag conformations across serotypes identified in this work support the assumption that a quadrivalent vaccine containing serotypes 2a and 3a could provide coverage against S. flexneri serotype 3b and serogroup 5. | en_US |
| dc.identifier | doi: 10.3390/vaccines8040643 | |
| dc.identifier.apacitation | Hlozek, J., Owen, S., Ravenscroft, N., & Kuttel, Michelle M. (2020). Molecular Modeling of the Shigella flexneri Serogroup 3 and 5 O-Antigens and Conformational Relationships for a Vaccine Containing Serotypes 2a and 3a. <i>Vaccines</i>, 8(4), http://hdl.handle.net/11427/35228 | en_ZA |
| dc.identifier.chicagocitation | Hlozek, Jason, Sara Owen, Neil Ravenscroft, and Michelle M. Kuttel "Molecular Modeling of the Shigella flexneri Serogroup 3 and 5 O-Antigens and Conformational Relationships for a Vaccine Containing Serotypes 2a and 3a." <i>Vaccines</i> 8, 4. (2020) http://hdl.handle.net/11427/35228 | en_ZA |
| dc.identifier.citation | Hlozek, J., Owen, S., Ravenscroft, N. & Kuttel, Michelle M. 2020. Molecular Modeling of the Shigella flexneri Serogroup 3 and 5 O-Antigens and Conformational Relationships for a Vaccine Containing Serotypes 2a and 3a. <i>Vaccines.</i> 8(4) http://hdl.handle.net/11427/35228 | en_ZA |
| dc.identifier.ris | TY - Journal Article AU - Hlozek, Jason AU - Owen, Sara AU - Ravenscroft, Neil AU - Kuttel, Michelle M. AB - The pathogenic bacterium Shigella flexneri is a leading global cause of diarrheal disease. The O-antigen is the primary vaccine target and distinguishes the 30 serotypes reported. Except for serotype 6, all S. flexneri serotypes have a common backbone repeating unit (serotype Y), with variations in substitution creating the various serotypes. A quadrivalent vaccine containing serotypes 2a and 3a (as well as 6 and Shigella sonnei) is proposed to provide broad protection against non-vaccine S. flexneri serotypes through shared epitopes and conformations. Here we model the O-antigen (O-Ag) conformations of serogroups 3 and 5: a continuation of our ongoing systematic study of the S. flexneri O-antigens that began with serogroup 2. Our simulations show that S. flexneri serogroups 2, 3, and 5 all have flexible O-Ags, with substitutions of the backbone altering the chain conformations in different ways. Our analysis suggests three general heuristics for the effects of substitution on the Shigella O-Ag conformations: (1) substitution on rhamnose C reduces the extension of the O-Ag chain; (2) substitution at O-3 of rhamnose A restricts the O-Ags to predominantly helical conformations, (3) substitution at O-3 of rhamnose B has only a slight effect on conformation. The common O-Ag conformations across serotypes identified in this work support the assumption that a quadrivalent vaccine containing serotypes 2a and 3a could provide coverage against S. flexneri serotype 3b and serogroup 5. DA - 2020-11-02 DB - OpenUCT DP - University of Cape Town IS - 4 J1 - Vaccines LK - https://open.uct.ac.za PY - 2020 T1 - Molecular Modeling of the Shigella flexneri Serogroup 3 and 5 O-Antigens and Conformational Relationships for a Vaccine Containing Serotypes 2a and 3a TI - Molecular Modeling of the Shigella flexneri Serogroup 3 and 5 O-Antigens and Conformational Relationships for a Vaccine Containing Serotypes 2a and 3a UR - http://hdl.handle.net/11427/35228 ER - | en_ZA |
| dc.identifier.uri | http://hdl.handle.net/11427/35228 | |
| dc.identifier.vancouvercitation | Hlozek J, Owen S, Ravenscroft N, Kuttel Michelle M. Molecular Modeling of the Shigella flexneri Serogroup 3 and 5 O-Antigens and Conformational Relationships for a Vaccine Containing Serotypes 2a and 3a. Vaccines. 2020;8(4) http://hdl.handle.net/11427/35228. | en_ZA |
| dc.language.iso | en | en_US |
| dc.publisher.department | Department of Chemistry | 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 | 4 | en_US |
| dc.source.journalvolume | 8 | en_US |
| dc.source.uri | https://www.mdpi.com/journal/vaccines | |
| dc.title | Molecular Modeling of the Shigella flexneri Serogroup 3 and 5 O-Antigens and Conformational Relationships for a Vaccine Containing Serotypes 2a and 3a | en_US |
| dc.type | Journal Article | en_US |