Cross-reactivity of Haemophilus influenzae type a and b polysaccharides: molecular modeling and conjugate immunogenicity studies.

Richardson, N. I. and Kuttel, M. M. and St Michael, F. and Carins, C. and Cox, A. D. and Ravenscroft, N. (2021) Cross-reactivity of Haemophilus influenzae type a and b polysaccharides: molecular modeling and conjugate immunogenicity studies., Glycoconjugate Journal, Springer Verlag (Germany).

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Abstract

Haemophilus influenzae is a leading cause of meningitis disease and mortality, particularly in young children. Since the introduction of a licensed conjugate vaccine (targeting the outer capsular polysaccharide) against the most prevalent serotype, Haemophilus influenzae serotype b, the epidemiology of the disease has changed and Haemophilus influenzae serotype a is on the rise, especially in Indigenous North American populations. Here we apply molecular modeling to explore the preferred conformations of the serotype a and b capsular polysaccharides as well as a modified hydrolysis resistant serotype b polysaccharide. Although both serotype b and the modified serotype b have similar random coil behavior, our simulations reveal some differences in the polysaccharide conformations and surfaces which may impact antibody cross-reactivity between these two antigens. Importantly, we find significant conformational differences between the serotype a and b polysaccharides, indicating a potential lack of cross-reactivity that is corroborated by immunological data showing little recognition or killing between heterologous serotypes. These findings support the current development of a serotype a conjugate vaccine.

Item Type:	Journal article (online only)
Subjects:	Computing methodologies > Modeling and simulation > Simulation types and techniques > Molecular simulation Applied computing > Physical sciences and engineering > Chemistry
Date Deposited:	03 Dec 2021 11:04
Last Modified:	03 Dec 2021 11:04
URI:	https://pubs.cs.uct.ac.za/id/eprint/1470

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