Cross-reactivity of Haemophilus influenzae type a and b polysaccharides: molecular modeling and conjugate immunogenicity studies
- 7 September 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Glycoconjugate Journal
- Vol. 38 (6), 735-746
- https://doi.org/10.1007/s10719-021-10020-0
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.Keywords
Funding Information
- University of Capetown
This publication has 55 references indexed in Scilit:
- Visualisation of cyclic and multi-branched molecules with VMDJournal of Molecular Graphics and Modelling, 2009
- Chapter 2 Quantifying Uncertainty and Sampling Quality in Biomolecular SimulationsAnnual Reports in Computational Chemistry, 2009
- CHARMM Additive All-Atom Force Field for Glycosidic Linkages between HexopyranosesJournal of Chemical Theory and Computation, 2009
- Additive empirical force field for hexopyranose monosaccharidesJournal of Computational Chemistry, 2008
- Scalable molecular dynamics with NAMDJournal of Computational Chemistry, 2005
- Molecular Dynamics Simulations of the Phosphodiester-Linked Repeating Units of the Haemophilus influenzae Types c and f Capsular PolysaccharidesThe Journal of Physical Chemistry B, 2001
- An NMR Spectroscopic Identity Test for the Control of the Capsular Polysaccharide from Haemophilus influenzae Type bBiologicals, 2000
- VMD: Visual molecular dynamicsJournal of Molecular Graphics, 1996
- A Leap-frog Algorithm for Stochastic DynamicsMolecular Simulation, 1988
- Comparison of simple potential functions for simulating liquid waterThe Journal of Chemical Physics, 1983