Vaccine-mediated protection against -associated enteric disease.

and 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, vaccine development has been hampered by the lack of animal models that recapitulate human disease pathogenesis. Here, we describe a naturally occurring -associated diarrhea model in outdoor-housed rhesus macaques. Using this model, we developed novel next-generation HO-based vaccines that induced strong antibacterial antibodies to multiple proteins including flagellin and provided up to 83% protection against severe -associated diarrhea. Whole-genome sequencing of circulating strains revealed little to no homology within lipooligosaccharide or capsular polysaccharide loci with the 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 -associated enteric disease.