CPS titers were measured 2 weeks after the third dose

CPS titers were measured 2 weeks after the third dose. efforts to develop protective measures against the pathogen are ongoing. One of the few defined virulence factors targeted for vaccine development is the capsule polysaccharide (CPS). We have developed a capsule conjugate vaccine againstC. jejunistrain 81-176 (CPS-CRM) that is immunogenic in mice and nonhuman primates (NHPs) but BS-181 HCl only moderately immunogenic in humans when delivered alone or with aluminium hydroxide. To enhance immunogenicity, two novel liposome-based adjuvant systems, the Army Liposome Formulation (ALF), made up of synthetic monophosphoryl lipid A, and ALF plus QS-21 (ALFQ), were evaluated with CPS-CRM in this study. In mice, ALF and ALFQ induced comparable amounts of CPS-specific IgG that was significantly higher than levels induced by CPS-CRM alone. Qualitative differences in antibody responses were observed where CPS-CRM alone induced Th2-biased IgG1, whereas ALF and ALFQ enhanced Th1-mediated anti-CPS IgG2b and IgG2c and generated functional bactericidal antibody titers. CPS-CRM + ALFQ was superior to vaccine alone or CPS-CRM + ALF in augmenting antigen-specific Th1, Th2, and Th17 cytokine responses and a significantly higher proportion of CD4+IFN-+IL-2+TNF-+and CD4+IL-4+IL-10+T cells. ALFQ also significantly enhanced anti-CPS responses in NHPs when delivered with CPS-CRM compared to alum- or ALF-adjuvanted groups and showed the highest protective efficacy against diarrhea following orogastric challenge withC. jejuni. This study provides evidence that this ALF adjuvants may provide enhanced immunogenicity of this and other novelC. jejunicapsule conjugate vaccines in humans. IMPORTANCECampylobacter jejuniis a leading cause of diarrheal disease worldwide, and currently no preventative interventions are available.C. jejuniis an invasive mucosal pathogen that has a variety of polysaccharide structures on its surface, including a capsule. In phase 1 studies, aC. jejunicapsule conjugate vaccine was safe but poorly immunogenic when delivered alone or with aluminium hydroxide. Here, we statement enhanced immunogenicity of the conjugate vaccine delivered with liposome adjuvants made up of monophosphoryl lipid A without or with QS-21, known as ALF and ALFQ, respectively, in preclinical studies. Both liposome adjuvants significantly enhanced immunity in mice and nonhuman primates and improved protective efficacy of the vaccine compared to alum in a nonhuman primateC. jejunidiarrhea model, providing encouraging evidence that these potent adjuvant formulations may enhance immunogenicity in upcoming human studies with thisC. jejuniconjugate and other malaria and HIV vaccine platforms. == INTRODUCTION == Campylobacterinfections are major causes of bacterial diarrhea worldwide, with the majority identified as being caused byCampylobacter jejuni.C. jejuniis a leading cause of foodborne illness BS-181 HCl in North America NKSF and Europe and was recognized in the Global Enteric Multicenter Study (GEMS) and Malnutrition and the Consequences for Child Health and Development Project (MAL-ED) multisite birth cohort studies BS-181 HCl as a significant attributable cause of severe-to-moderate diarrhea that is associated with growth stunting in middle-to-low-income countries (14).C. jejuniinfection typically results in acute inflammatory gastroenteritis that is self-limiting, but in more severe cases, the disease can progress to dysentery. In addition to acute disease,C. jejuniinfections are associated with long-term sequelae, including reactive arthritis, inflammatory bowel syndrome, and most frequently with Guillain-Barr syndrome (GBS) (59). GBS is usually caused by development of autoantibodies to a subset ofC. jejunistrains that express lipooligosaccharides (LOS) that mimic human gangliosides in structure, and it is currently estimated thatC. jejuniinfection precedes GBS in 20 to 50% of cases in the developed world and in other regions may be even higher (8). The global burden imposed by the morbidity ofCampylobacterdisease and its related sequelae drives efforts to develop protective interventions. Steps to influence disease prevention, including source eradication, personal protective measures, and chemoprophylaxis, have been moderately successful thus far. Moreover, the rise of antibiotic-resistantC. jejunipoint to the need for other types of interventions (1012). You will find no licensed vaccines available forCampylobacter. One crucial hurdle in BS-181 HCl vaccine development is usually that, unlike other enteric pathogens, you will find few defined virulence factors that have been targeted as subunit vaccine methods.C. jejuniexpresses a polysaccharide capsule (CPS) that is the major serodeterminant of the Penner heat-stable (HS) serotyping plan (13). You will find 47 known HS serotypes ofC. BS-181 HCl jejuniresulting from 35 chemically diverse CPS structures (14,15). Importantly, CPS has been shown to be an important virulence factor modulating invasion and disease and contributing to serum resistance (16,17). We have.