Vaccine-mediated protection against Campylobacter -associated enteric disease

Abstract

Campylobacter coli and Campylobacter jejuni 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, Campylobacter vaccine development has been hampered by the lack of animal models that recapitulate human disease pathogenesis. Here, we describe a naturally occurring Campylobacter-associated diarrhea model in outdoor-housed rhesus macaques. Using this model, we developed novel next-generation H2O2-based Campylobacter vaccines that induced strong antibacterial antibodies to multiple Campylobacter proteins including flagellin and provided up to 83% protection against severe C. coli–associated diarrhea. Whole-genome sequencing of circulating Campylobacter strains revealed little to no homology within lipooligosaccharide or capsular polysaccharide loci with the Campylobacter 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 Campylobacter-associated enteric disease.

Reduced infant rhesus macaque growth rates due to environmental enteric dysfunction and association with histopathology in the large intestine

“…We examined naturally occurring enteric disease among outdoor-housed rhesus macaques at the Oregon National Primate Research Center (ONPRC) and the California National Primate Research Center (CNPRC) 16 – 19 . The animals are housed in family groups of 25–100 individuals with access to clean water and balanced nutrition.…”

“…Group-housed rhesus macaques provide an important model for the study of naturally acquired human enteric disease 16 – 19 . These animals have gut microbiomes 21 – 23 that are similar to those observed among people living in resource-poor settings under conditions of poor sanitation and hygiene and are endemically exposed to enteric pathogens associated with human growth stunting, including Campylobacter , Shigella , ETEC, Cryptosporidium , E. histolytica , and Giardia (Fig.…”

Growth faltering regardless of chronic diarrhea is associated with mucosal immune dysfunction and microbial dysbiosis in the gut lumen

“…Rhesus macaques are the gold standard model for the study of several infectious diseases due to their genetic and physiological similarity to humans. Rhesus macaques housed at the Oregon National Primate Research Center (ONPRC) and California National Primate Research Center (CNPRC) naturally develop the diarrheal disease at a predictable yearly rate with Campylobacter and Shigella being the primary pathogens isolated at clinic admission 36 – 38 . In addition, infant macaques that experience diarrhea suffer growth faltering 37 .…”

Development of a next-generation chikungunya virus vaccine based on the HydroVax platform

“…We [8][9][10][11][12] and others [13,14] have previously described a simple H 2 O 2 -based inactivation platform for the development of new and improved vaccines, including a next-generation version of this approach that incorporates a site-directed oxidation technique that provides more rapid pathogen inactivation while maintaining antigenic structures [15,16]. Here, this advanced inactivation technology was applied to the development of a CHIKV vaccine and compared to other common inactivation methodologies.…”