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Open AccessArticle

Molecular Modeling of the Shigella flexneri Serogroup 3 and 5 O-Antigens and Conformational Relationships for a Vaccine Containing Serotypes 2a and 3a

1
Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa
2
Department of Computer Science, University of Cape Town, Rondebosch 7701, South Africa
*
Author to whom correspondence should be addressed.
Vaccines 2020, 8(4), 643; https://doi.org/10.3390/vaccines8040643
Received: 16 September 2020 / Revised: 9 October 2020 / Accepted: 29 October 2020 / Published: 2 November 2020
(This article belongs to the Special Issue Carbohydrate Immunogens in Vaccines)
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. View Full-Text
Keywords: O-antigen; conformation; Shigella flexneri; molecular modelling; cross protection O-antigen; conformation; Shigella flexneri; molecular modelling; cross protection
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Hlozek, J.; Owen, S.; Ravenscroft, N.; Kuttel, M.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, 643.

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