Campylobacter jejuni infection is now the main cause of diarrhea-related illnesses in humans. An efficacious vaccine for the traveler and developing world market would be welcomed. We are engaged in the discovery and characterization of serotype-specific C. jejuni capsule polysaccharides (CPSs) to study their role in virulence and as protective vaccine antigens. Our prototype conjugate vaccine with serotype HS23 CPS (strain 81-176) has been shown to fully protect non-human primates against diarrhea inflicted by C. jejuni HS23, but ultimately, a useful CPS-based vaccine will have to be multivalent. To this end, we describe here the creation of a CPS-conjugate vaccine against C. jejuni serotype HS15. Structural analysis revealed that a repeating block consisting of l-α-arabinofuranose (Ara) and 6-deoxy-l-α-gulo-heptopyranose (6d-gulo-Hep) comprised the CPS of serotype HS15 type strain ATCC 43442 [→3)-α-L-Araf-(1→3)-6d-l-α-gulo-Hepp(1→](n). Strategically, the non-reducing end of the CPS was activated and used in the attachment of CPS to CRM(197) to yield a conjugate vaccine. A serological assessment of the CPS(HS15)-CRM(197) conjugate with an anti-HS15 polyclonal antibody confirmed the conservation of antigenic epitopes, and subsequent inoculation of mice with CPS(HS15)-CRM(197) revealed that this conjugate was indeed capable of raising anti-CPS(HS15) antibodies.
Campylobacter jejuni, capsule polysaccharide, conjugate vaccine, Diarrheal vaccine, 6-deoxy-gulo-heptose
NCBI PubMed ID: 23261782Publication DOI: 10.1016/j.carres.2012.11.017Journal NLM ID: 0043535Publisher: Elsevier
Correspondence: M.A. Monteiro
Institutions: Department of Chemistry, University of Guelph, Guelph, Ontario, Canada N1G 2W1
Methods: 13C NMR, 1H NMR, NMR-2D, methylation, GC-MS, SDS-PAGE, composition analysis, NMR-1D, immunoblotting, periodate oxidation, conjugation
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