Campylobacter jejuni polysaccharides and conjugate vaccines thereof
Campylobacter jejuni' infections have been recognized as major cause of human gastroenteritis worldwide and can lead to more severe neurological disorders such as Guillain-Barre? and Miller-Fisher syndromes. The capsular polysaccharides of 'C. jejuni' are thought to play a role in disease pathogenesis, and antibodies to the capsular entities have been detected in humans. In this research, the structures of capsular polysaccharides of the following 'C. jejuni' serotypes were investigated to involve in a multivalent vaccine development: serotypes HS:1 (strain 856); HS:3,13,50 (strain BH-01-0142); HS:4,13,64 (CG8486); HS:4 type strain (strain 854); HS:13 (strain 3019); HS:23,36 (strains PG3208 and CG8421); HS:44 (strain 2871); and HS:1,44 (strain 3087) were structurally characterized by a series of chemical and analytical methods, including gas-liquid chromatography mass spectrometry, and nuclear magnetic resonance spectrometry. The structural data revealed that the 'C. jejuni' possesses the ability to incorporate heptoses of unusual configuration as key components of capsule polysaccharides. These heptose components appear to play a strong immunogenic role in that they were observed to control the serospecificity of capsular polysaccharides. Glycoconjugates vaccines composed of part of the above mentioned ' C. jejuni' capsular polysaccharides and the carrier protein, diphtheria toxin CRM197, were synthesized by appropriate oxidations followed by coupling methods, and were evaluated for immunogenicity and protection efficacy in mice and non-human primates. Of particular note, the prototype ' C. jejuni' capsule conjugate vaccine CPSPG3208-CRM 197 (PG3208= serotype HS:23,36) was shown to fully protect non-human primates ('Aotus monkeys') against 'C. jejuni' induced diarrhea. More importantly, it was observed that this CPSPG3208 -CRM197 conjugate vaccine was capable of cross-protecting the animals against diarrheal diseases when challenged with another strains of serotype HS:23,36 complex (strain CG8421). The lipooligosaccharides of two 'C. jejuni' strains, HS:3,13,50 (strain BH-01-0142) and HS:23,36 (strain CG8421) that are to be used in human challenged models, were analyzed to confirm the absence of sialic acid (a requirement for a challenge strain to avoid autoimmunity). Interestingly, the two lipooligosaccharides generated identical structures containing an unique monosaccharide residue, quinovosamine.