Vaccine-mediated protection against <i>Campylobacter</i> -associated enteric disease

Abstract

<i>Campylobacter coli</i> and <i>Campylobacter jejuni</i> are responsible for 400 million to 500 million cases of enteric disease each year and represent the most common cause of bacterial gastroenteritis worldwide. Despite its global importance, <i>Campylobacter</i> vaccine development has been hampered by the lack of animal models that recapitulate human disease pathogenesis. Here, we describe a naturally occurring <i>Campylobacter</i>-associated diarrhea model in outdoor-housed rhesus macaques. Using this model, we developed novel next-generation H₂O₂-based <i>Campylobacter</i> vaccines that induced strong antibacterial antibodies to multiple <i>Campylobacter</i> proteins including flagellin and provided up to 83% protection against severe <i>C. coli</i>-associated diarrhea. Whole-genome sequencing of circulating <i>Campylobacter</i> strains revealed little to no homology within lipooligosaccharide or capsular polysaccharide loci with the <i>Campylobacter</i> vaccine strains used in these studies, indicating that vaccine-mediated immunity was not restricted to a single homologous serotype. Together, these results demonstrate an important advance in vaccine development and a new approach to reducing <i>Campylobacter</i>-associated enteric disease.