Status of vaccine research and development for Campylobacter jejuni

Abstract

Campylobacter jejuni is one of the leading causes of bacterial diarrhea worldwide and is associated with a number of sequelae, including Guillain-Barre Syndrome, reactive arthritis, irritable bowel syndrome and growth stunting/malnutrition. Vaccine development against C. jejuni is complicated by its antigenic diversity, a lack of small animal models, and a poor understanding of the bacterium's pathogenesis. Vaccine approaches have been limited to recombinant proteins, none of which have advanced beyond Phase I testing. Genomic analyses have revealed the presence of a polysaccharide capsule on C. jejuni. Given the success of capsule-conjugate vaccines for other mucosal pathogens of global importance, efforts to evaluate this established approach for C. jejuni are also being pursued. A prototypical capsule-conjugate vaccine has demonstrated efficacy against diarrheal disease in non-human primates and is currently in Phase I testing. In addition to proof of concept studies, more data on the global prevalence of capsular types, and a better understanding of the acute and chronic consequences of C. jejuni are needed to inform investments for a globally relevant vaccine.

Current and Potential Treatments for Reducing Campylobacter Colonization in Animal Hosts and Disease in Humans

“…Unfortunately, antibodies directed against these mimics may cross-react with human peripheral nerves, which is the pathogenic basis of GBS. Thus, whole cell oral vaccines that are at times logical for developing protection against other enteric pathogens, are not the preferred approach for vaccine development against Campylobacter (Riddle and Guerry, 2016). Regardless, a whole cell vaccine was developed, but it was unsuccessful in a phase 2b challenge with C. jejuni 81–176 (Tribble et al, 2008).…”

“…ACE Biosciences developed a protein subunit vaccine that was determined to be non-effective in phase 2b trials (Maue et al, 2014). Another recent study showed that a recombinant non-glycosylated C. jejuni flagellin was poorly immunogenic in Phase I trials and would likely not be effective (Riddle and Guerry, 2016). Schumack et al developed a conjugate vaccine against the Campylobacter capsule polysaccharide (CPS) that conferred 100% protection against diarrhea from a homologous C. jejuni strain in a NHP model (Schumack et al, 2016).…”

“…As such, only a small fraction of all vaccine candidates reach the market (Jensen et al, 2014). In addition to these more general challenges, Campylobacter vaccine development is currently hindered by an incomplete comprehension of their protective epitopes, antigenic diversity, pathogenesis, and their association with post-infectious syndromes such as irritable bowel syndrome, reactive arthritis, and GBS (Riddle and Guerry, 2016). …”

The Periplasmic Chaperone Network of Campylobacter jejuni: Evidence that SalC (Cj1289) and PpiD (Cj0694) Are Involved in Maintaining Outer Membrane Integrity

“…As a strategically important food-borne pathogen, novel interventions are required to reduce the numbers of campylobacters in the human food-chain. As well as increased bio-security measures, targeted interventions such as poultry vaccines (recently reviewed by Riddle and Guerry, 2016) and the use of specific anti- Campylobacter agents or probiotics (Saint-Cyr et al, 2016) on farm have been proposed, but will require identification of appropriate targets and increased knowledge of C. jejuni physiology respectively.…”

The PAS Domain-Containing Protein HeuR Regulates Heme Uptake in Campylobacter jejuni

“…Patients with C. jejuni infection typically develop mild to severe, bloody diarrhea that may be accompanied by fever. Additionally, several postinfectious disorders have been associated with C. jejuni infection, including Guillain-Barre Syndrome, postinfectious irritable bowel syndrome, and reactive arthritis (2, 3). Further highlighting these concerns is increasing resistance of C. jejuni to the clinically relevant antibiotics azithromycin and ciprofloxacin, prompting the Centers for Disease Control and Prevention to list antibiotic-resistant C. jejuni as a “serious threat” to public health (1).…”