scholarly journals A Listeria monocytogenes-Based Vaccine Formulation Reduces Vertical Transmission and Leads to Enhanced Pup Survival in a Pregnant Neosporosis Mouse Model

Vaccines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1400
Author(s):  
Dennis Imhof ◽  
William Robert Pownall ◽  
Camille Monney ◽  
Anna Oevermann ◽  
Andrew Hemphill
Keyword(s):  
Listeria Monocytogenes ◽  
Mouse Model ◽  
Neospora Caninum ◽  
Post Partum ◽  
Systemic Infection ◽  
Surface Protein ◽  
Control Group ◽  
Protective Effects ◽  
Igg Antibody ◽  
Th2 Response

The apicomplexan parasite Neospora caninum is the worldwide leading cause of abortion and stillbirth in cattle. An attenuated mutant Listeria monocytogenes strain (Lm3Dx) was engineered by deleting the virulence genes actA, inlA, and inlB in order to avoid systemic infection and to target the vector to antigen-presenting cells (APCs). Insertion of sag1, coding for the major surface protein NcSAG1 of N. caninum, yielded the vaccine strain Lm3Dx_NcSAG1. The efficacy of Lm3Dx_NcSAG1 was assessed by inoculating 1 × 105, 1 × 106, or 1 × 107 CFU of Lm3Dx_NcSAG1 into female BALB/c mice by intramuscular injection three times at two-week intervals, and subsequent challenge with 1 × 105N. caninum tachyzoites of the highly virulent NcSpain-7 strain on day 7 of pregnancy. Dose-dependent protective effects were seen, with a postnatal offspring survival rate of 67% in the group treated with 1 × 107 CFU of Lm3Dx_NcSAG1 compared to 5% survival in the non-vaccinated control group. At euthanasia (25 days post-partum), IgG antibody titers were significantly decreased in the groups receiving the two higher doses and cytokines recall responses in splenocyte culture supernatants (IFN-γ, IL-4, and IL-10) were increased in the vaccinated groups. Thus, Lm3Dx_NcSAG1 induces immune-protective effects associated with a balanced Th1/Th2 response in a pregnant neosporosis mouse model and should be further assessed in ruminant models.

scholarly journals The Protective Effects of Acer okamotoanum and Isoquercitrin on Obesity and Amyloidosis in a Mouse Model

Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1353
Author(s):  
Ji Hyun Kim ◽  
Sanghyun Lee ◽  
Eun Ju Cho
Keyword(s):  
Body Weight ◽  
Mouse Model ◽  
High Fat Diet ◽  
Ethyl Acetate Fraction ◽  
Control Group ◽  
Protective Effects ◽  
High Fat ◽  
Acer Okamotoanum ◽  
Related Proteins ◽  
The Brain

Obesity increases risk of Alzheimer’s Disease (AD). A high fat diet (HFD) can lead to amyloidosis and amyloid beta (Aβ) accumulation, which are hallmarks of AD. In this study, protective effects of the ethyl acetate fraction of Acer okamotoanum (EAO) and isoquercitrin were evaluated on obesity and amyloidosis in the HFD- and Aβ-induced mouse model. To induce obesity and AD by HFD and Aβ, mice were provided with HFD for 10 weeks and were intracerebroventricularly injected with Aβ25–35. For four weeks, 100 and 10 mg/kg/day of EAO and isoquercitrin, respectively, were administered orally. Administration of EAO and isoquercitrin significantly decreased body weight in HFD and Aβ-injected mice. Additionally, EAO- and isoquercitrin-administered groups attenuated abnormal adipokines release via a decrease in leptin and an increase in adiponectin levels compared with the control group. Furthermore, HFD and Aβ-injected mice had damaged liver tissues, but EAO- and isoquercitrin-administered groups attenuated liver damage. Moreover, administration of EAO and isoquercitrin groups down-regulated amyloidosis-related proteins in the brain such as β-secretase, presenilin (PS)-1 and PS-2 compared with HFD and Aβ-injected mice. This study indicated that EAO and isoquercitrin attenuated HFD and Aβ-induced obesity and amyloidosis, suggesting that they could be effective in preventing and treating both obesity and AD.

scholarly journals Transcytosis of Listeria monocytogenes across the intestinal barrier upon specific targeting of goblet cell accessible E-cadherin

2011 ◽  
Vol 208 (11) ◽  
pp. 2263-2277 ◽  
Author(s):  
Georgios Nikitas ◽  
Chantal Deschamps ◽  
Olivier Disson ◽  
Théodora Niault ◽  
Pascale Cossart ◽  
...  
Keyword(s):  
Listeria Monocytogenes ◽  
Intestinal Epithelium ◽  
Foodborne Pathogen ◽  
Intestinal Barrier ◽  
Systemic Infection ◽  
Surface Protein ◽  
Intestinal Lumen ◽  
Specific Host ◽  
Species Specific ◽  
E Cadherin

Listeria monocytogenes (Lm) is a foodborne pathogen that crosses the intestinal barrier upon interaction between its surface protein InlA and its species-specific host receptor E-cadherin (Ecad). Ecad, the key constituent of adherens junctions, is typically situated below tight junctions and therefore considered inaccessible from the intestinal lumen. In this study, we investigated how Lm specifically targets its receptor on intestinal villi and crosses the intestinal epithelium to disseminate systemically. We demonstrate that Ecad is luminally accessible around mucus-expelling goblet cells (GCs), around extruding enterocytes at the tip and lateral sides of villi, and in villus epithelial folds. We show that upon preferential adherence to accessible Ecad on GCs, Lm is internalized, rapidly transcytosed across the intestinal epithelium, and released in the lamina propria by exocytosis from where it disseminates systemically. Together, these results show that Lm exploits intrinsic tissue heterogeneity to access its receptor and reveal transcytosis as a novel and unanticipated pathway that is hijacked by Lm to breach the intestinal epithelium and cause systemic infection.

scholarly journals Evaluation of recombinant Brachyspira pilosicoli oligopeptide-binding proteins as vaccine candidates in a mouse model of intestinal spirochaetosis

2010 ◽  
Vol 59 (3) ◽  
pp. 353-359 ◽  
Author(s):  
Abdolreza Movahedi ◽  
David J. Hampson
Keyword(s):  
Mouse Model ◽  
Binding Proteins ◽  
Control Group ◽  
Cumulative Number ◽  
Igg Antibody ◽  
Brachyspira Pilosicoli ◽  
Distribution Study ◽  
Different Strains

The anaerobic intestinal spirochaete Brachyspira pilosicoli colonizes the large intestine of humans, and various species of animals and birds, in which it may induce a mild colitis and diarrhoea. The aim of the current study was to evaluate the use of putative oligopeptide-binding proteins of B. pilosicoli as vaccine components. A partial genome sequence of B. pilosicoli porcine strain 95/1000 was subjected to bioinformatics analysis, and six genes predicted to encode oligopeptide-binding proteins were selected. Following a PCR-based distribution study of the genes across different strains of the spirochaete, they were amplified from B. pilosicoli human strain WesB and cloned in Escherichia coli. The recombinant histidine-tagged proteins were purified and subjected to in vitro and in vivo immunogenicity analysis. Recombinant products (P-1 and P-3) from two genes that were immunogenic and recognized by sera from pigs that had recovered from B. pilosicoli infections were tested in a mouse model of intestinal spirochaetosis. For each recombinant protein, groups of 12 C3H/HeJ mice were vaccinated subcutaneously with 100 μg protein emulsified in Freund's incomplete adjuvant, twice with a 2 week interval. Two weeks later the vaccinated and non-vaccinated control animals were challenged orally with B. pilosicoli strain WesB. Both proteins induced systemic and local colonic IgG antibody responses, and, following experimental infection, the cumulative number of colonization days was significantly (P<0.001) less in both groups of vaccinated mice compared to the control mice. There were significantly (P=0.012) fewer mice colonized in the group vaccinated with P-1 than in the non-vaccinated control group. The results suggest that oligopeptide-binding proteins may have potential for use as components of vaccines for B. pilosicoli.

scholarly journals Protective Immunity Against Neospora caninum Infection Induced by 14-3-3 Protein in Mice

2021 ◽  
Vol 8 ◽  
Author(s):  
Shan Li ◽  
Nan Zhang ◽  
Shaoxiong Liu ◽  
Jianhua Li ◽  
Li Liu ◽  
...  
Keyword(s):  
Immune Responses ◽  
Vaccine Development ◽  
Neospora Caninum ◽  
Survival Rates ◽  
Parasite Burden ◽  
Mouse Serum ◽  
Protective Effects ◽  
Igg Antibody ◽  
Caninum Infection ◽  
Ifn Γ

Neospora caninum is an apicomplexan parasite that infects many mammals and remains a threatening disease worldwide because of the lack of effective drugs and vaccines. Our previous studies demonstrated that N. caninum 14-3-3 protein (Nc14-3-3), which is included in N. caninum extracellular vesicles (NEVs), can induce effective immune responses and stimulate cytokine expression in mouse peritoneal macrophages. However, whether Nc14-3-3 has a protective effect and its mechanisms are poorly understood. Here, we evaluated the immune responses and protective effects of Nc14-3-3 against exposure to 2 × 107 Nc-1 tachyzoites. Antibody (IgG, IgGl, and IgG2a) levels and Th1-type (IFN-γ and IL-12) and Th2-type (IL-4 and IL-10) cytokines in mouse serum, survival rates, survival times, and parasite burdens were detected. In the present study, the immunostimulatory effect of Nc14-3-3 was confirmed, as it triggered Th1-type cytokine (IFN-γ and IL-12) production in mouse serum 2 weeks after the final immunization. Moreover, the immunization of C57BL/6 mice with Nc14-3-3 induced high IgG antibody levels and significant increases in CD8+ T lymphocytes in the spleens of mice, indicating that the cellular immune response was significantly stimulated. Mouse survival rates and times were significantly prolonged after immunization; the survival rates were 40% for Nc14-3-3 immunization and 60% for NEV immunization, while mice that received GST, PBS, or blank control all died at 13, 9, or 8 days, respectively, after intraperitoneal N. caninum challenge. In addition, qPCR analysis indicated that there was a reduced parasite burden and diminished pathological changes in the mice immunized with Nc14-3-3. Our data demonstrate that vaccination of mice with Nc14-3-3 elicits both cellular and humoral immune responses and provides partial protection against acute neosporosis. Thus, Nc14-3-3 could be an effective antigen candidate for vaccine development for neosporosis.

scholarly journals Protective Immunity Induced by Virus-Like Particle Containing Merozoite Surface Protein 9 of Plasmodium berghei

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 428
Author(s):  
Su-Hwa Lee ◽  
Hae-Ji Kang ◽  
Ki-Back Chu ◽  
Swarnendu Basak ◽  
Dong-Hun Lee ◽  
...  
Keyword(s):  
T Cell ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Effector Memory ◽  
Cell Populations ◽  
Control Group ◽  
Igg Antibody ◽  
Erythrocyte Invasion ◽  
Virus Like Particle ◽  
Parasite Replication

Merozoite surface protein 9 (MSP-9) from Plasmodium has shown promise as a vaccine candidate due to its location and possible role in erythrocyte invasion. In this study, we generated virus-like particles (VLPs) targeting P. berghei MSP-9, and investigated the protection against lethal doses of P. berghei in a mouse model. We found that VLP vaccination induced a P. berghei-specific IgG antibody response in the sera and CD4+ and CD8+ T cell populations in blood compared to a naïve control group. Upon challenge infection with P. berghei, vaccinated mice showed a significant increase in CD4+ and CD8+ effector memory T cell and memory B cell populations. Importantly, MSP-9 VLP immunization inhibited levels of the pro-inflammatory cytokines IFN-γ and IL-6 in the spleen and parasite replication in blood, resulting in significantly prolonged survival time. These results suggest that the MSP-9 VLP vaccine may constitute an effective malaria vaccine.

scholarly journals Immunization with Recombinant Sao Protein Confers Protection against Streptococcus suis Infection

2007 ◽  
Vol 14 (8) ◽  
pp. 937-943 ◽  
Author(s):  
Yuanyi Li ◽  
Marcelo Gottschalk ◽  
Miriam Esgleas ◽  
Sonia Lacouture ◽  
J. Daniel Dubreuil ◽  
...  
Keyword(s):  
Clinical Signs ◽  
Surface Protein ◽  
Streptococcus Suis ◽  
Cross Protection ◽  
Antibody Responses ◽  
Control Group ◽  
Igg Antibody ◽  
Tissue Samples ◽  
Vitro Assay

ABSTRACT Sao is a Streptococcus suis surface protein recently identified as a potential vaccine candidate. In this study, recombinant Sao in combination with Quil A provided cross-protection against S. suis serotype 2 disease in mouse and pig vaccination protocols. Subcutaneous immunization of mice elicited strong immunoglobulin G (IgG) antibody responses. All four IgG subclasses were induced, with the IgG2a titer being the highest, followed by those of IgG1, IgG2b, and IgG3. Challenge of the mice with S. suis strain 31533 resulted in a mortality rate of 80% for the control group, which received Quil A only. In contrast, all of the mice immunized with Sao survived. In a pig vaccination protocol, intramuscular immunization with Sao also elicited significant humoral antibody responses, and both the IgG1 and IgG2 subclasses were induced, with a predominance of IgG2 production. In vitro assay showed that Sao-induced antibodies significantly promoted the ability of porcine neutrophils in opsonophagocytic killing of S. suis. An aerosol challenge of the pigs with S. suis strain 166 resulted in clinical signs characteristic of S. suis infection in diseased pigs. The vaccine group showed significantly better survival, lower clinical scores, and less S. suis recovery from postmortem tissue samples than did the control group. Furthermore, this study also revealed that although challenge S. suis strains express Sao size variants, recombinant Sao conferred cross-protection. These data demonstrate that recombinant Sao formulated with Quil A triggers strong opsonizing antibody responses which confer efficient immunity against challenge infection with heterologous S. suis type 2.

Withdrawn: Hepatoprotective effects of Tribulus terrestris L. (Zygophyllales: Zygophyllaceae) hydro-alcholic extract on non-alcoholic fatty liver-induced rats

2016 ◽  
Vol 3 (5) ◽  
pp. 143
Author(s):  
Fatemeh Almasi ◽  
Mozafar Khazaei ◽  
Shima Chehrei ◽  
Ali Ghanbari
Keyword(s):  
Fatty Liver ◽  
Liver Tissue ◽  
Serum Lipid ◽  
Histopathological Examination ◽  
Serum Levels ◽  
Lipid Profiles ◽  
Control Group ◽  
Tribulus Terrestris ◽  
Protective Effects ◽  
Alcoholic Fatty Liver

Non-alcoholic fatty liver induces many complications to the liver tissue and also serum related parameters. Medicinal plants are the safe therapeutic strategy for the treatment of diseases. In this regards, the present study was conducted to evaluate the effect of Tribulus terrestris L. (Zygophyllales: Zygophyllaceae) extract on non-alcoholic fatty liver in rats. In this experimental study, thirty male Wistar rats were divided into five groups (n = 6). Animals in experimental groups were received high fructose diet (70%) (HDF) daily alone or in combined with daily intraperitoneal injection of 500, 700 and 1,000 mg/kg extract of T. terrestris. Control group of rats was feed with standard chow. The serum levels of biomarkers of liver and serum lipid profiles were assessed, also histopathological examination of liver tissue done. Data were analyzed using One-way ANOVA method followed by Tukey’s post-hoc multiple comparison test and P < 0.05 was considered statistically significant. There were significant improvements for biomarkers of liver tissue (P < 0.05) and serum lipid profiles (P < 0.01) in the HFD-fed rats that were treated with T. terrestris extract compare to HFD-fed group. In addition, accumulation of lipids in hepatocytes was significantly reduced in the HFD-fed + extract administrated groups in comparison to HFD-fed rats (P < 0.01). T. terrestris extract has protective effects against non-alcoholic fatty liver by changing biomarkers of liver tissue, serum lipid profiles and histopathological anomalies of liver tissue, to normal range.

scholarly journals Newly Developed Recombinant Antithrombin Protects the Endothelial Glycocalyx in an Endotoxin-Induced Rat Model of Sepsis

2020 ◽  
Vol 22 (1) ◽  
pp. 176
Author(s):  
Toshiaki Iba ◽  
Jerrold H. Levy ◽  
Koichiro Aihara ◽  
Katsuhiko Kadota ◽  
Hiroshi Tanaka ◽  
...  
Keyword(s):  
Dose Group ◽  
Low Dose ◽  
Leukocyte Adhesion ◽  
Endothelial Glycocalyx ◽  
High Dose Group ◽  
Control Group ◽  
High Dose ◽  
Protective Effects ◽  
Circulating Levels

(1) Background: The endothelial glycocalyx is a primary target during the early phase of sepsis. We previously reported a newly developed recombinant non-fucosylated antithrombin has protective effects in vitro. We further evaluated the effects of this recombinant antithrombin on the glycocalyx damage in an animal model of sepsis. (2) Methods: Following endotoxin injection, in Wistar rats, circulating levels of hyaluronan, syndecan-1 and other biomarkers were evaluated in low-dose or high-dose recombinant antithrombin-treated animals and a control group (n = 7 per group). Leukocyte adhesion and blood flow were evaluated with intravital microscopy. The glycocalyx was also examined using side-stream dark-field imaging. (3) Results: The activation of coagulation was inhibited by recombinant antithrombin, leukocyte adhesion was significantly decreased, and flow was better maintained in the high-dose group (both p < 0.05). Circulating levels of syndecan-1 (p < 0.01, high-dose group) and hyaluronan (p < 0.05, low-dose group; p < 0.01, high-dose group) were significantly reduced by recombinant antithrombin treatment. Increases in lactate and decreases in albumin levels were significantly attenuated in the high-dose group (p < 0.05, respectively). The glycocalyx thickness was reduced over time in control animals, but the derangement was attenuated and microvascular perfusion was better maintained in the high-dose group recombinant antithrombin group (p < 0.05). (4) Conclusions: Recombinant antithrombin maintained vascular integrity and the microcirculation by preserving the glycocalyx in this sepsis model, effects that were more prominent with high-dose therapy.

scholarly journals Protective Effects of Polyphenol Enriched Complex Plants Extract on Metabolic Dysfunctions Associated with Obesity and Related Nonalcoholic Fatty Liver Diseases in High Fat Diet-Induced C57BL/6 Mice

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 302
Author(s):  
Ahtesham Hussain ◽  
Jin Sook Cho ◽  
Jong-Seok Kim ◽  
Young Ik Lee
Keyword(s):  
Body Weight ◽  
Blood Glucose ◽  
Mouse Model ◽  
High Fat Diet ◽  
Liver Diseases ◽  
Liver Weight ◽  
Control Group ◽  
High Fat ◽  
Herbal Formulation ◽  
Plants Extract

Background: Currently, obesity is a global health challenge due to its increasing prevalence and associated health risk. It is associated with various metabolic diseases, including diabetes, hypertension, cardiovascular disease, stroke, certain forms of cancer, and non-alcoholic liver diseases (NAFLD). Objective: The aim of this study to evaluate the effects of polyphenol enriched herbal complex (Rubus crataegifolius/ellagic acid, Crataegus pinnatifida Bunge/vitexin, chlorogenic acid, Cinnamomum cassiaa/cinnamic acid) on obesity and obesity induced NAFLD in the high-fat diet (HFD)-induced obese mouse model. Methods: Obesity was induced in male C57BL/6 mice using HFD. After 8 weeks, the mice were treated with HFD+ plants extract for 8 weeks. Body weight, food intake weekly, and blood sugar level were measured. After sacrifice, changes in the treated group’s liver weight, fat weight, serum biochemical parameters, hormone levels, and enzyme levels were measured. For histological analysis, tissues were stained with hematoxylin-eosin (H&E) and Oil Red-O. Results: Our results showed that the herbal complex ameliorated body weight and liver weight gain, and decreased total body fat in HFD-fed animals. Post prandial blood glucose (PBG) and fasting blood glucose (FBG) were lower in the herbal complex-treated group than in the HFD control group. Additionally, herbal formulation treatment significantly increased HDL levels in serum and decreased TC, TG, AST, ALT, deposition of fat droplets in the liver, and intima media thickness (IMT) in the aorta. Herbal complex increased serum adiponectin and decreased serum leptin. Herbal complex also increased carnitine palmityl transferase (CPT) activity and significantly decreased enzyme activity of beta-hydroxy beta methyl glutamyl-CoA (HMG-CoA) reductase, and fatty acid synthase (FAS). Conclusions: The results of this study demonstrated that the herbal complex is an effective herbal formulation in the attenuation of obesity and obesity-induced metabolic dysfunction including NAFLD in HFD-induced mouse model.

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