Functional complement-fixing antibodies are generated against a Campylobacter jejuni capsule conjugate vaccine in non-human primates

Abstract

Abstract Campylobacter jejuni is among the most common causes of diarrheal disease worldwide and efforts to develop protective measures against the pathogen are ongoing. One of the few defined virulence factors targeted for vaccine development is the capsule polysaccharide (CPS). We have developed a capsule conjugate vaccine against a prototype CPS, type HS23/36, that confers 100% protection against diarrhea caused by a homologous strain of C. jejuni in a non-human primate (NHP) model; however the mechanisms of protection remain unknown. Other licensed capsule conjugate vaccines against encapsulated gram-negative organisms use bactericidal antibody titers as a correlate of protection. We developed a flow cytometry-based serum bactericidal assay (SBA) to determine if increased levels of complement-fixing antibodies correlate with protection against C. jejuni. Sera from NHPs immunized with HS23/36 CPS-CRM197 vaccine showed significantly higher SBA titers when compared with control NHPs. Results were similar to those of a bacteriological-based SBA. All NHPs, irrespective of immune status, that did not develop diarrhea, had higher SBA titers compared with NHPs that developed diarrhea. Importantly, a strong correlation was found between serum anti-CPS IgG and SBA titers in NHPs and similar studies will be conducted in upcoming human clinical trials. This flow cytometry-based SBA assay is much simpler than bacteriological-based assays and should facilitate analyses of functional antibodies against multivalent C. jejuni capsule conjugate vaccines.