scholarly journals Dissecting serotype-specific contributions to live oral cholera vaccine efficacy

2020 ◽  
Author(s):  
Brandon Sit ◽  
Bolutife Fakoya ◽  
Ting Zhang ◽  
Gabriel Billings ◽  
Matthew K. Waldor
Keyword(s):  
Protective Efficacy ◽  
Oral Vaccines ◽  
Germ Free ◽  
O Antigen ◽  
Immunodominant Antigen ◽  
Oral Cholera Vaccine ◽  
Experimental Approaches ◽  
Selection For ◽  
The Impact ◽  
Strain Dependent

AbstractThe O1 serogroup of Vibrio cholerae causes pandemic cholera and is divided into Ogawa and Inaba serotypes. The O-antigen is V. cholerae’s immunodominant antigen, and the two serotypes, which differ by the presence or absence of a terminally methylated O-antigen, likely influence development of immunity to cholera and oral cholera vaccines (OCVs). However, there is no consensus regarding the relative immunological potency of each serotype, in part because previous studies relied on genetically heterogenous strains. Here, we engineered matched serotype variants of a live OCV candidate, HaitiV, and used a germ-free mouse model to evaluate the immunogenicity and protective efficacy of each vaccine serotype. By combining vibriocidal antibody quantification with single and mixed strain infection assays, we found that all three HaitiV variants - InabaV, OgawaV, and HikoV (bivalent Inaba/Ogawa) - were immunogenic and protective, suggesting the impact of O1 serotype variation on OCV function may be minimal. The potency of OCVs was found to be challenge strain-dependent, emphasizing the importance of appropriate strain selection for cholera challenge studies. Our findings and experimental approaches will be valuable for guiding the development of live OCVs and oral vaccines for additional pathogens.

scholarly journals Dissecting serotype-specific contributions to live oral cholera vaccine efficacy

2021 ◽  
Vol 118 (7) ◽  
pp. e2018032118
Author(s):  
Brandon Sit ◽  
Bolutife Fakoya ◽  
Ting Zhang ◽  
Gabriel Billings ◽  
Matthew K. Waldor
Keyword(s):  
Protective Efficacy ◽  
Oral Vaccines ◽  
Live Vaccines ◽  
O Antigen ◽  
Immunodominant Antigen ◽  
Oral Cholera Vaccine ◽  
Experimental Approaches ◽  
Selection For ◽  
The Impact ◽  
Strain Dependent

The O1 serogroup of Vibrio cholerae causes pandemic cholera and is divided into the Ogawa and Inaba serotypes. The O-antigen is V. cholerae’s immunodominant antigen, and the two serotypes, which differ by the presence or absence of a terminally methylated O-antigen, likely influence development of immunity to cholera and oral cholera vaccines (OCVs). However, there is no consensus regarding the relative immunological potency of each serotype, in part because previous studies relied on genetically heterogeneous strains. Here, we engineered matched serotype variants of a live OCV candidate, HaitiV, and used a germfree mouse model to evaluate the immunogenicity and protective efficacy of each vaccine serotype. By combining vibriocidal antibody quantification with single- and mixed-strain infection assays, we found that all three HaitiV variants—InabaV, OgawaV, and HikoV (bivalent Inaba/Ogawa)—were immunogenic and protective. None of the vaccine serotypes were superior across both of these vaccine metrics, suggesting that the impact of O1-serotype variation in OCV design, although detectable, is subtle. However, all three live vaccines significantly outperformed formalin-killed HikoV, supporting the idea that live OCV usage will bolster current cholera control practices. The potency of OCVs was found to be challenge strain-dependent, emphasizing the importance of appropriate strain selection for cholera challenge studies. Our findings and experimental approaches will be valuable for guiding the development of live OCVs and oral vaccines for additional pathogens.

scholarly journals Salmonella enterica Serovar Typhi Lipopolysaccharide O-Antigen Modification Impact on Serum Resistance and Antibody Recognition

2017 ◽  
Vol 85 (4) ◽  
Author(s):  
Erica Kintz ◽  
Christian Heiss ◽  
Ian Black ◽  
Nicholas Donohue ◽  
Naj Brown ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Protective Efficacy ◽  
Bacterial Pathogen ◽  
Phase Variation ◽  
Gram Negative ◽  
Content Type ◽  
Immune Evasion Mechanism ◽  
Antibody Recognition ◽  
O Antigen ◽  
Immunodominant Antigen

ABSTRACT Salmonella enterica serovar Typhi is a human-restricted Gram-negative bacterial pathogen responsible for causing an estimated 27 million cases of typhoid fever annually, leading to 217,000 deaths, and current vaccines do not offer full protection. The O-antigen side chain of the lipopolysaccharide is an immunodominant antigen, can define host-pathogen interactions, and is under consideration as a vaccine target for some Gram-negative species. The composition of the O-antigen can be modified by the activity of glycosyltransferase (gtr) operons acquired by horizontal gene transfer. Here we investigate the role of two gtr operons that we identified in the S. Typhi genome. Strains were engineered to express specific gtr operons. Full chemical analysis of the O-antigens of these strains identified gtr-dependent glucosylation and acetylation. The glucosylated form of the O-antigen mediated enhanced survival in human serum and decreased complement binding. A single nucleotide deviation from an epigenetic phase variation signature sequence rendered the expression of this glucosylating gtr operon uniform in the population. In contrast, the expression of the acetylating gtrC gene is controlled by epigenetic phase variation. Acetylation did not affect serum survival, but phase variation can be an immune evasion mechanism, and thus, this modification may contribute to persistence in a host. In murine immunization studies, both O-antigen modifications were generally immunodominant. Our results emphasize that natural O-antigen modifications should be taken into consideration when assessing responses to vaccines, especially O-antigen-based vaccines, and that the Salmonella gtr repertoire may confound the protective efficacy of broad-ranging Salmonella lipopolysaccharide conjugate vaccines.

scholarly journals E. coli Enterotoxin LtB Enhances Vaccine-Induced Anti-H. pylori Protection by Promoting Leukocyte Migration into Gastric Mucus via Inflammatory Lesions

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 982
Author(s):  
Xiaoyan Peng ◽  
Rongguang Zhang ◽  
Chen Wang ◽  
Feiyan Yu ◽  
Mingyang Yu ◽  
...  
Keyword(s):  
Cellular Immunity ◽  
Protective Efficacy ◽  
Gastric Injury ◽  
Oral Vaccines ◽  
Gastric Mucus ◽  
E Coli ◽  
Non Invasive ◽  
Considerable Impact ◽  
H Pylori

Current studies indicate that the anti-H. pylori protective efficacy of oral vaccines to a large extent depends on using mucosal adjuvants like E. coli heat-lable enterotoxin B unit (LtB). However, the mechanism by which Th17/Th1-driven cellular immunity kills H. pylori and the role of LtB remains unclear. Here, two L. lactis strains, expressing H. pylori NapA and LtB, respectively, were orally administrated to mice. As observed, the administration of LtB significantly enhanced the fecal SIgA level and decreased gastric H. pylori colonization, but also markedly aggravated gastric inflammatory injury. Both NapA group and NapA+LtB group had elevated splenocyte production of IL-8, IL-10, IL-12, IL-17, IL-23 and INF-γ. Notably, gastric leukocytes’ migration or leakage into the mucus was observed more frequently in NapA+LtB group than in NapA group. This report is the first that discusses how LtB enhances vaccine-induced anti-H. pylori efficacy by aggravating gastric injury and leukocytes’ movement into the mucus layer. Significantly, it brings up a novel explanation for the mechanism underlying mucosal cellular immunity destroying the non-invasive pathogens. More importantly, the findings suggest the necessity to further evaluate LtB’s potential hazards to humans before extending its applications. Thus, this report can provide considerable impact on the fields of mucosal immunology and vaccinology.

scholarly journals Identifying Critical Binder Attributes to Facilitate Binder Selection for Efficient Formulation Development in a Continuous Twin Screw Wet Granulation Process

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 210
Author(s):  
Lise Vandevivere ◽  
Maxine Vangampelaere ◽  
Christoph Portier ◽  
Cedrine de Backere ◽  
Olaf Häusler ◽  
...  
Keyword(s):  
Dissolution Kinetics ◽  
Wet Granulation ◽  
Continuous Manufacturing ◽  
Formulation Development ◽  
Granulation Process ◽  
Low Viscosity ◽  
Twin Screw ◽  
Poorly Soluble ◽  
Selection For ◽  
The Impact

The suitability of pharmaceutical binders for continuous twin-screw wet granulation was investigated as the pharmaceutical industry is undergoing a switch from batch to continuous manufacturing. Binder selection for twin-screw wet granulation should rely on a scientific approach to enable efficient formulation development. Therefore, the current study identified binder attributes affecting the binder effectiveness in a wet granulation process of a highly soluble model excipient (mannitol). For this formulation, higher binder effectiveness was linked to fast activation of the binder properties (i.e., fast binder dissolution kinetics combined with low viscosity attributes and good wetting properties by the binder). As the impact of binder attributes on the granulation process of a poorly soluble formulation (dicalcium phosphate) was previously investigated, this enabled a comprehensive comparison between both formulations in current research focusing on binder selection. This comparison revealed that binder attributes that are important to guide binder selection differ in function of the solubility of the formulation. The identification of critical binder attributes in the current study enables rational and efficient binder selection for twin-screw granulation of well soluble and poorly soluble formulations. Binder addition proved especially valuable for a poorly soluble formulation.

scholarly journals The Self-Enforcing Starch–Gluten System—Strain–Dependent Effects of Yeast Metabolites on the Polymeric Matrix

Polymers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 30
Author(s):  
Thekla Alpers ◽  
Viviane Tauscher ◽  
Thomas Steglich ◽  
Thomas Becker ◽  
Mario Jekle
Keyword(s):  
Strain Hardening ◽  
Polymer System ◽  
Rheological Behaviour ◽  
Rate Dependency ◽  
Lower Strain ◽  
End Point Rate ◽  
The Impact ◽  
Elongational Rheometry ◽  
Strain Dependent ◽  
Strain Hardening Index

The rheological behaviour of dough during the breadmaking process is strongly affected by the accumulation of yeast metabolites in the dough matrix. The impact of metabolites in yeasted dough-like concentrations on the rheology of dough has not been characterised yet for process-relevant deformation types and strain rates, nor has the effect of metabolites on strain hardening behaviour of dough been analysed. We used fundamental shear and elongational rheometry to study the impact of fermentation on the dough microstructure and functionality. Evaluating the influence of the main metabolites, the strongest impact was found for the presence of expanding gas cells due to the accumulation of the yeast metabolite CO2, which was shown to have a destabilising impact on the surrounding dough matrix. Throughout the fermentation process, the polymeric and entangled gluten microstructure was found to be degraded (−37.6% average vessel length, +37.5% end point rate). These microstructural changes were successfully linked to the changing rheological behaviour towards a highly mobile polymer system. An accelerated strain hardening behaviour (+32.5% SHI for yeasted dough) was promoted by the pre-extension of the gluten strands within the lamella around the gas cells. Further, a strain rate dependency was shown, as a lower strain hardening index was observed for slow extension processes. Fast extension seemed to influence the disruption of sterically interacting fragments, leading to entanglements and hindered extensibility.

A NONLINEAR STRAIN-DEPENDENT VARIABLE-ORDER FRACTIONAL MODEL WITH APPLICATIONS TO ALUMINUM FOAMS

Fractals ◽  
2021 ◽  
Author(s):  
WEI CAI ◽  
PING WANG
Keyword(s):  
Power Law ◽  
Variable Order ◽  
Aluminum Foams ◽  
Static Compression ◽  
Fractional Model ◽  
Comparative Results ◽  
The Impact ◽  
Strain Responses ◽  
Strain Dependent ◽  
Quasi Static Compression

In this paper, a power-law strain-dependent variable order is first incorporated into the fractional constitutive model and employed to describe mechanical behaviors of aluminum foams under quasi-static compression and tension. Comparative results illustrate that power-law strain-dependent variable order is capable of better describing stress–strain responses compared with the traditional linear one. The evolution of fractional order along with the porosities or relative densities can be well qualitatively interpreted by its physical meaning. Furthermore, the model is also extended to characterize the impact behaviors under large constant strain rates. It is observed that fractional model with sinusoidal variable order agrees well with the experimental data of aluminum foams with impact and non-impact surfaces.

Genetic Diversity of Cronobacter sakazakii Isolates Collected from a Swiss Infant Formula Production Facility

2013 ◽  
Vol 76 (5) ◽  
pp. 883-887 ◽  
Author(s):  
ANDREA MÜLLER ◽  
ROGER STEPHAN ◽  
CLAUDIA FRICKER-FEER ◽  
ANGELIKA LEHNER
Keyword(s):  
Infant Formula ◽  
Monitoring Program ◽  
Sequence Type ◽  
Powdered Infant Formula ◽  
Cronobacter Sakazakii ◽  
Production Facility ◽  
Pfge Analysis ◽  
O Antigen ◽  
Selection For ◽  
Prevalent Species

In this study, 141 Cronobacter isolates that were collected based on a hygienic monitoring program performed in a powdered infant formula production facility in Switzerland between September 2011 and October 2012 were further characterized. Isolates were identified to the species level by molecular methods, and strains of Cronobacter sakazakii were further subtyped by applying PCR-based O-antigen serotyping, multilocus sequence typing (MLST), and pulsed-field gel electrophoresis (PFGE). C. sakazakii was the most prevalent species identified (93.6%). Among this collection of isolates, representatives of all but one O-antigen serotype (serotype O5) were recognized. MLST analysis of 19 selected isolates revealed that most of the typeable isolates belonged to sequence type (ST) 4. Correlations between ST4 and serotype O2 and between ST83 and serotype O7 were observed. PFGE analysis revealed clusters with multiple isolates, including strains from samples collected at different time points and sampling sources. Generally, the observed heterogeneity among strains collected over the 13 months of the monitoring program was high, suggesting a constant flux among strains rather than a selection for persisting organisms.

scholarly journals The Impact of Selection using Residual Average Daily Gain and Marbling EPDs on Growth Performance and Carcass Traits in Angus Steers

2019 ◽  
Vol 3 (2) ◽  
Author(s):  
T. R. Krause ◽  
E. R. Moore ◽  
J. Duggin ◽  
J. R. Segers ◽  
T. D. Pringle
Keyword(s):  
Growth Performance ◽  
Feed Efficiency ◽  
Average Daily Gain ◽  
Backfat Thickness ◽  
Feeding Trial ◽  
Body Weights ◽  
Selection For ◽  
Carcass Merit ◽  
The Impact ◽  
Daily Gain

ObjectivesProfitability in the beef industry has narrow margins regulated by revenue from output traits like growth and carcass merit, but profitability is also largely impacted by input expenses like feed costs. Selecting for improvements in feed efficiency during the finishing phase, one of the most feed intensive segments of the industry, can help to mitigate those input costs. This study compared growth performance, feed efficiency, body composition, and carcass characteristics in Angus steers (n = 321) from bulls divergently selected for feed efficiency and marbling.Materials and MethodsAngus sires were selected based on high (10th percentile or better) and low (85th percentile or worse) residual average daily gain (RADG) EPD as well as high (fifth percentile or better) and average (near 50th percentile) marbling (MARB) EPD. These criteria resulted in a 2 × 2 factorial design with four breeding lines: high RADG/high MARB, high RADG/average MARB, low RADG/high MARB, low RADG/average MARB. Data were analyzed using MIXED procedures of SAS with RADG and MARB as main effects. Significance was set at α = 0.05. Generation was also analyzed, where generation one (GEN1) steers were from a selected sire while generation two (GEN2) steers were from a selected sire and a selected dam.ResultsUltrasound and carcass data revealed no differences (P ≥ 0.12) in 12th rib backfat thickness from weaning through slaughter for the RADG EPD groups. Yield grade and dressing percent did not differ (P ≥ 0.56) across RADG or MARB groups. At the beginning and end of the feeding trial, the high RADG (P ≤ 0.02) group had larger ultrasound ribeye area (REA) than the low RADG group. Carcass REA tended (P = 0.08) to be larger in the high versus low RADG steers. During the feedlot trial and through slaughter, body weight was heavier (P ≤ 0.006) for the high versus low RADG steers but did not differ (P ≥ 0.44) across MARB EPD. Feed efficiency measures did not differ (P ≥ 0.32) across RADG or MARB groups apart from the tendency (P = 0.08) for residual feed intake to be lower in the high versus low RADG steers. Marbling scores differed (P ≤ 0.04) across RADG and MARB groups with the low RADG steers and the high MARB steers having improved marbling. The quality grade distribution across MARB EPD revealed that the average MARB steers graded 73% Choice and 25% Prime while the high MARB steers graded 56% and 42%, respectively. Slice shear force did not differ (P ≥ 0.32) across RADG or MARB EPD. Body weights tended (P = 0.06) to be heavier at the start of the feeding trial for GEN1 versus GEN2 steers. Total gain, average daily gain, and feed to gain (F:G) differed by generation (P ≤ 0.007) with increased rates of gain and reduced F:G in the GEN2 versus GEN1 steers. Body weights did not differ (P = 0.72) across GEN at the end of the feeding trial. Backfat thickness at the start and end of the feedlot phase was less (P ≤ 0.03) and marbling score was improved (P = 0.02) in the GEN2 versus GEN1 steers, respectively.ConclusionThese results suggest that selection using RADG EPD has negligible impacts on meat quality; and that progress in selection for efficiency can be achieved while advancing carcass quality and value. Furthermore, continued divergent selection for feed efficiency and marbling has the potential to improve feed efficiency through advancements in the rate of gain, while enhancing carcass merit through marbling.

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