Oral Presentation Australian & New Zealand Society of Magnetic Resonance Conference 2017

Structural insights guiding the design of a vaccine candidate against Otitis Media pathogens (#79)

Sanjesh Singh 1 2 , Martin Frank 3 , Patrick M. Collins 1 , Ian R. Peak 1 , I. Darren Grice 1 , Jennifer Wilson 2
  1. Institute for Glycomics, Gold Coast campus, Griffith University, Queensland
  2. Menzies Health Institute and School of Medical Science, Gold Coast campus, Griffith University, Queensland
  3. Biognos AB, Generatorsgatan , Gothenburg, Sweden

Otitis media is a very common childhood infection of the middle ear caused predominantly a cocktail of bacteria including Moraxella catarrhalis, Streptococcus pneumoniae and Haemophilis influenzae.  Repeated episodes of otitis media can lead to hearing loss and developmental issues in young infants. Moreover, recently an oligosaccharide antigen from Moraxella catarrhalis and a protein antigen from Haemophilus influenzae have been combined into a single vaccine candidate and tested for their ability to invoke an immune response in a mouse model.  The results of these investigations will be presented. In addition, we have used NMR and molecular modelling to study the conformation of potential carbohydrate antigens derived from the oligosaccharide component of the lipooligosccharide from M. catarrahlis.  These studies show that the highly-branched glucose-rich inner core of the oligosaccharide has an altered conformation compared to the most truncated tetra-glucose-Kdo lgt1/4Δ oligosaccharide (OS) structure. Addition of one residue each to the (1-4) and (1-6) chains to give the lgt2Δ oligosaccharide is the minimum requirement for this conformational change to occur.  The occurrence of a significant conformational change between a truncated and extended OS structure may have important implications on the strategy utilized to design carbohydrate vaccines composed of truncated OS that, although may contain the core residues common to many strains, may not necessary possess the same 3D structure of a wild type OS.  The results of extensive molecular modeling and NMR investigations showing significantly altered conformational preferences between the two structures will be presented.