Flagellin is a Th1 polarizing factor for human CD4+ T cells and induces protection in a murine neonatal vaccination model of rotavirus infection

Neonates have an increased susceptibility to infections, particularly those caused by intracellular pathogens, leading to high morbidity and mortality rates. This is partly because of a poor response of neonatal CD4⁺ T cells, leading to deficient antibody production and a low production of IFN-γ, resulting in deficient elimination of intracellular pathogens. The poor memory response of human neonates has underpinned the need for improving vaccine formulations. Molecular adjuvants that improve the response of neonatal lymphocytes, such as the ligands of toll-like receptors (TLRs), are attractive candidates. Among them, flagellin, the TLR5 ligand, is effective at very low doses; prior immunity to flagellin does not impair its adjuvant activity. Human CD4⁺ and CD8⁺ T cells express TLR5. We found that flagellin induces the expression of IFN-γ, IL-1β and IL-12 in mononuclear cells from human neonate and adult donors. When human naïve CD4⁺ T cells were activated in the presence of flagellin, there was high level of expression of IFN-γ in both neonates and adults. Furthermore, flagellin induced IFN-γ production in Th1 cells obtained from adult donors; in the Th2 population, it inhibited IL-4 cytokine production. Flagellin also promoted expression of the IFN-γ receptor in naive CD4⁺ T cells from neonates and adults. To test the adjuvant capacity of flagellin in vivo, we used a murine neonate vaccination model for infection with rotavirus, a pathogen responsible for severe diarrhea in young infants. Using the conserved VP6 antigen, we observed an 80% protection against rotavirus infection in the presence of flagellin, but only in those mice previously primed in the neonatal period. Our data suggest that flagellin could be an attractive adjuvant for achieving a Th1 response.     

Parental perceptions,attitudes and acceptance of childhood immunization in Saudi Arabia: A cross sectional study

ObjectivesThe widespread availability and use of vaccines have tremendously reduced morbidity, mortality and health care costs associated with infectious diseases. However, parental beliefs about vaccination are one of the major factors in achieving high vaccination rates. Thus, this study aims to assess the perceptions and attitudes regarding routine childhood immunization among Saudi parents.MethodsA cross sectional study with a pre-tested 18-item questionnaire was conducted using 467 randomly selected parents from the Hail region of Saudi Arabia in the period between February 1st, 2016, and February 1st, 2017. The validated questionnaire consisted of three sections that collected information on participants’ demographics, parents’ awareness of vaccine benefits, and parents’ practices regarding the immunization of their children.ResultsFemale and male parents comprised 54.5% (255) and 45.5% (212) of the sample, respectively, and the response and completion rates were 97%. The majority of the respondents had received a formal education (94.1%, 439), were gainfully employed (62.9%, 294) and had a regular monthly income (73.3%). The majority of the respondents were aware of childhood vaccinations (78.9%), completed vaccinations mandated for children up to 5 years (86.2%), encouraged other parents to do so (89.9%), and had easy access to vaccines (90.5%). Sixty to ninety percent of the respondents were knowledgeable regarding the health benefits of vaccinations in children, even though 18.4% of their children had experienced vaccination-related minor adverse effects during or after vaccination of which 23.2% required doctor's visits. Health care professionals were the most frequent source of parents’ vaccine-related information (65.2%), and vaccination reminder services provided by the Ministry of Health (MOH) via mobile phones were cited by 57.5% of respondents.ConclusionsConfidence in and acceptance of childhood vaccinations, perceptions of vaccine-related health benefits and ease of access to immunizations appeared to be quite good among Saudi parents.     

Evaluation of the protective efficacy of four newly identified surface proteins of Erysipelothrix rhusiopathiae

Erysipelothrix rhusiopathiae is the causative agent of animal erysipelas and human erysipeloid. Bacterial surface proteins are promising vaccine candidates. We recently identified 3 E. rhusiopathiae surface proteins (GAPDH, HP0728, and HP1472) and characterized their roles as virulence factors. However, their efficacy as protective antigens is still unknown. The N-terminal region of a previously identified surface protein, CbpB (CbpB-N), is speculated to be a protective antigen, but this needs to be verified. The aim of this study was to evaluate the protective efficacy of GAPDH, HP0728, HP1472, and CbpB-N. Immunization with recombinant GAPDH provided complete protection in a mouse model, recombinant CbpB-N provided partial protection, while recombinant HP0728 and HP1472 provided no protection. Recombinant GAPDH also provided good protection in a pig model. GAPDH antiserum exhibited significant blood bactericidal activity against E. rhusiopathiae. In conclusion, GAPDH and CbpB-N were found to be protective antigens of E. rhusiopathiae, and GAPDH is a promising vaccine candidate.     

High incidence of group A rotaviruses G4P[6] strains among children in Gyeonggi province of South Korea,from 2009 to 2012

The genotype distribution of group A rotaviruses (RVAs) circulating in Gyeonggi province, South Korea between 2009 and 2012 was investigated. A total of 2619 stool specimens from sporadic acute gastroenteritis cases and 117 acute gastroenteritis outbreaks were analyzed. Among them, RVAs were detected from 263 (10.0%) sporadic cases and 3 (2.6%) outbreaks. The G4P[6] strains predominated (29.7%), followed by G1P[8] (19.4%), G2P[4] (15.6%), G3P[8] (13.3%) and G9P[8] (6.5%) strain. Especially 96.2% of the genotype G4P[6] strains were isolated from children < 1 year of age. Phylogenetic analysis revealed that genotype G4P[6] strains were members of sub-lineage Ie(G4) and Ia(P[6]). Intensified monitoring of RVAs, especially G4P[6] strains among young children, is essential to control RVA infections.     

Effects of a moderately high-protein diet and interval aerobic training combined with strength-endurance exercise on markers of bone metabolism,microarchitecture and turnover in obese Zucker rats

BackgroundWeight loss is a public health concern in obesity-related diseases such as metabolic syndrome, and the protein level of the diets seem to be crucial for the development and maintenance of bone. The nature of exercise and whether exercise in combination with moderately high-protein dietary interventions could protect against potential bone mass deficits remains unclear.ObjectivesTo investigate the effects of a moderately high-protein diet and interval aerobic training combined with strength-endurance exercise (IASE) protocol on bone status, and to assess potential interaction effects (i.e. diet*IASE).MethodsMale Zucker fatty rats were randomized distributed into 4 groups (n = 8): normoprotein + sedentary; normoprotein + exercise; moderately high-protein + sedentary, and moderately high-protein + exercise. Training groups conducted an IASE program, 5 days/week for 2 months. Markers of bone metabolism were measured in plasma. Parameters of bone mass and 3D outcomes for trabecular and cortical bone microarchitecture were assessed by micro-computed tomography.ResultsFemur length, plasma osteocalcin, sclerostin, osteoprotegerin, receptor activator of nuclear factor kappa-B ligand, insulin, leptin, PTH, uric acid and urinary phosphorus levels were lower in the moderately high-protein compared to the normoprotein groups (all, p < 0.05), whereas plasma alkaline phosphatase, aspartate aminotransferase, alanine transaminase, and urinary uric acid concentrations, and cortical total volume (TV) and bone volume (BV) were higher in the moderately high-protein (all, p < 0.01). Final body weight and alkaline phosphatase levels were lower in the exercise compared to the sedentary (both, p < 0.05), whereas femur length and weight, aminoterminal propeptides of type I procollagen and C-terminal telopeptides of type I collagen concentrations, and cortical TV and BV were higher in the exercise compared to the sedentary groups (all, p < 0.05).ConclusionThe combination of interventions may be effective to enhance trabecular bone microarchitecture and BMD, and has a partial impact on cortical bone in obese rats. Nevertheless, they do not induce any alteration on the bone turnover markers.