Campylobacter jejuniCapsule Polysaccharide Conjugate Vaccine

Campylobacter jejuni is one of the most common causes of human diarrheal disease worldwide. Campylobacteriosis cases are primarily sporadic, but outbreaks are not uncommon. In developed countries Campylobacteriosis cases are about 50/100,000 per year, but in developing countries, particularly in Southeast Asia, the incidence is estimated to be at least 10 times higher. In these endemic regions, this high incidence represents a life threatening risk, especially towards the pediatric population. C. jejuni is considered a zoonotic disease in which the major source of contamination is through the consumption of poultry. In humans, the infectious dose can be as low as 500-1,000 bacteria with symptoms being variable and dependent on the bacterial strain and host factors. Some patients only present mild abdominal pain and mild to no diarrhea, while the most severe cases are associated with severe abdominal cramping, accompanied with fever, headaches, myalgia, and large volumes of mucous and bloody diarrhea that can last for several days. If left untreated, severe C. jejuni cases can be lethal. C. jejuni infections have also been associated with the development of Guillain-Barré syndrome (an autoimmune disease triggered by C. jejuni lipooligosaccharide sub-structures that mimic glanglioside forms) inflammatory bowel syndrome, reactive arthritis and stunting in children from developing countries. In this piece, we describe the development of a C. jejuni vaccine candidate in which the protective antigens are the cell-surface capsular polysaccharides (CPSs), with focus on (i) CPS discovery highlighting the two key structural features of C. jejuni CPSs, 6-deoxy-heptoses of unsual configurations and variably linked O-methyl-phosphoramidate moities; (ii) conjugation of C. jejuni CPSs to carrier proteins using new methodology for CPS activation (TEMPO-mediated oxidation); and (iii) protection studies in a non-human primate model. Collectively, the data obtained has allowed us to advance our prototype C. jejuni CPS conjugate vaccine through cGMP production and onto an ongoing phase I human clinical trial.