The design of a capsule polysaccharide conjugate vaccine against Campylobacter jejuni serotype HS15

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 CRM197 to yield a conjugate vaccine. A serological assessment of the CPSHS15–CRM197 conjugate with an anti-HS15 polyclonal antibody confirmed the conservation of antigenic epitopes, and subsequent inoculation of mice with CPSHS15–CRM197 revealed that this conjugate was indeed capable of raising anti-CPSHS15 antibodies.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Serospecificity of Campylobacter jejuni serotype HS15 based on structure with arabinose and 6-deoxy-gulo-heptose. ► Selective conjugation of Campylobacter jejuni HS15 capsule to CRM197 through the non-reducing end. ► The capsule HS15 conjugate is immunoreactive against HS15 whole cell polyclonal antibody. ► The CPSHS15–CRM197 conjugate is immunogenic in mice.