| Abstract | Haemophilus infuenzae 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 infuenzae serotype b, the epidemiology of the disease has changed and Haemophilus infuenzae 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 modifed hydrolysis resistant serotype b polysaccharide. Although both serotype b and the modifed serotype b have similar random coil behavior, our simulations reveal some diferences in the polysaccharide conformations and surfaces which may impact antibody cross-reactivity between these two antigens. Importantly, we fnd signifcant conformational diferences 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 fndings support the current development of a serotype a conjugate vaccine. |
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