Molecular modeling of Group B Streptococcus type II and III capsular polysaccharides explains low filter retention of type II and lack of cross-reactivity with type III

Richardson, N. I. and Berti, F. and Ravenscroft, N. and Kuttel, M. M. (2025) Molecular modeling of Group B Streptococcus type II and III capsular polysaccharides explains low filter retention of type II and lack of cross-reactivity with type III, Carbohydrate Polymers, 367, 123964, Elsevier.

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Abstract

Group B Streptococcus (GBS) is a bacterial pathogen associated with significant morbidity and mortality in pregnant women and infants, particularly in resource-limited settings. A hexavalent vaccine candidate in development incorporates the capsular polysaccharides (CPSs) from the most prevalent serotypes: Ia, Ib, II, III, IV, and V. Vaccine production is facilitated by a standardized CPS purification process. In the final purification step, a 30 kDa membrane filter gives high-yield recovery for five of the six CPSs, but <50 % for type II (GBSII), despite similar CPS structure and size. However, a smaller 10 kDa membrane improves recovery to about 90 %, suggesting that CPS conformation affects retention. Here comparative molecular modeling – corroborated by through-space NMR correlations – reveals that GBSII forms compact, globular conformations, while type III (GBSIII) forms an elongated zig-zag. This explains GBSII's poor retention during filtration: GBSII's compact globules pass through the 30 kDa membrane more easily than GBSIII's elongated forms. Additionally, we identify distinct epitopes and compare their interactions with a GBSIII-specific fragment antibody to clarify the lack of cross-reactivity between GBSII and GBSIII. This work provides valuable mechanistic insight into physically observed behavior to inform development of multivalent GBS vaccines to reduce maternal and infant mortality.

Item Type:	Journal article (paginated)
Uncontrolled Keywords:	Capsular polysaccharide; Carbohydrate epitopes; Conformation; Cross-protection; Group B Streptococcus; Molecular modeling; Vaccine processing
Subjects:	Computing methodologies > Modeling and simulation Computing methodologies > Modeling and simulation > Simulation types and techniques > Molecular simulation Applied computing > Physical sciences and engineering > Chemistry
Date Deposited:	13 Oct 2025 12:36
Last Modified:	13 Oct 2025 12:36
URI:	https://pubs.cs.uct.ac.za/id/eprint/1756

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