A Bioprocessed Polysaccharide from Lentinus edodes Mycelia Cultures with Turmeric Protects Chicks from a Lethal Challenge of Salmonella Gallinarum

2017 ◽  
Vol 80 (2) ◽  
pp. 245-250 ◽  
Author(s):  
Dalmuri Han ◽  
Hyung Tae Lee ◽  
June Bong Lee ◽  
Yongbaek Kim ◽  
Sang Jong Lee ◽  
...  
Keyword(s):  
Lethal Dose ◽  
Water Extract ◽  
Biologically Active ◽  
Feed Additive ◽  
Lentinus Edodes ◽  
T Helper 1 ◽  
Lethal Challenge ◽  
Salmonella Gallinarum ◽  
Salmonella Infections

ABSTRACT Our previous studies demonstrated that a bioprocessed polysaccharide (BPP) isolated from Lentinus edodes mushroom mycelia cultures supplemented with black rice bran can protect mice against Salmonella lipopolysaccharide–induced endotoxemia and reduce the mortality from Salmonella Typhimurium infection through upregulated T-helper 1 immunity. Here, we report that a BPP from L. edodes mushroom mycelia liquid cultures supplemented with turmeric (referred to as BPP-turmeric) alters chicken macrophage responses against avian-adapted Salmonella Gallinarum and protects chicks against a lethal challenge from Salmonella Gallinarum. In vitro analyses revealed that the water extract of BPP-turmeric (i) changed the protein expression or secretion profile of Salmonella Gallinarum, although it was not bactericidal, (ii) reduced the phagocytic activity of the chicken-derived macrophage cell line HD-11 when infected with Salmonella Gallinarum, and (iii) significantly activated the transcription expression of interleukin (IL)-1β, IL-10, tumor necrosis factor α, and inducible nitric oxide synthase in response to various Salmonella infections, whereas it repressed that of IL-4, IL-6, interferon-β, and interferon-γ. We also found that BPP-turmeric (0.1 g/kg of feed) as a feed additive provided significant protection to 1-day-old chicks infected with a lethal dose of Salmonella Gallinarum. Collectively, these results imply that BPP-turmeric contains biologically active component(s) that protect chicks against Salmonella Gallinarum infection, possibly by regulating macrophage immune responses. Further studies are needed to evaluate the potential efficacy of BPP-turmeric as a livestock feed additive for the preharvest control of fowl typhoid or foodborne salmonellosis.

scholarly journals A Chimeric Protein That Functions as both an Anthrax Dual-Target Antitoxin and a Trivalent Vaccine

2010 ◽  
Vol 54 (11) ◽  
pp. 4750-4757 ◽  
Author(s):  
Gaobing Wu ◽  
Yuzhi Hong ◽  
Aizhen Guo ◽  
Chunfang Feng ◽  
Sha Cao ◽  
...  
Keyword(s):  
Protective Antigen ◽  
Vaccine Candidate ◽  
Lethal Factor ◽  
Lethal Dose ◽  
Chimeric Protein ◽  
Dominant Negative ◽  
Lethal Challenge ◽  
Edema Factor ◽  
Trivalent Vaccine

ABSTRACT Effective measures for the prophylaxis and treatment of anthrax are still required for counteracting the threat posed by inhalation anthrax. In this study, we first demonstrated that the chimeric protein LFn-PA, created by fusing the protective antigen (PA)-binding domain of lethal factor (LFn) to PA, retained the functions of the respective molecules. On the basis of this observation, we attempted to develop an antitoxin that targets the binding of lethal factor (LF) and/or edema factor (EF) to PA and the transportation of LF/EF. Therefore, we replaced PA in LFn-PA with a dominant-negative inhibitory PA (DPA), i.e., PAF427D. In in vitro models of anthrax intoxication, the LFn-DPA chimera showed 3-fold and 2-fold higher potencies than DPA in protecting sensitive cells against anthrax lethal toxin (LeTx) and edema toxin (EdTx), respectively. In animal models, LFn-DPA exhibited strong potency in rescuing mice from lethal challenge with LeTx. We also evaluated the immunogenicity and immunoprotective efficacy of LFn-DPA as an anthrax vaccine candidate. In comparison with recombinant PA, LFn-DPA induced significantly higher levels of the anti-PA immune response. Moreover, LFn-DPA elicited an anti-LF antibody response that could cross-react with EF. Mice immunized with LFn-DPA tolerated a LeTx challenge that was 5 times its 50% lethal dose. Thus, LFn-DPA represents a highly effective trivalent vaccine candidate for both preexposure and postexposure vaccination. Overall, we have developed a novel and dually functional reagent for the prophylaxis and treatment of anthrax.

scholarly journals INFECTION-IMMUNITY IN EXPERIMENTAL SALMONELLOSIS

1966 ◽  
Vol 124 (4) ◽  
pp. 601-619 ◽  
Author(s):  
F. M. Collins ◽  
G. B. Mackaness ◽  
R. V. Blanden
Keyword(s):  
Salmonella Enteritidis ◽  
Lethal Dose ◽  
Acquired Resistance ◽  
Challenge Dose ◽  
Salmonella Gallinarum ◽  
Degree Of Protection ◽  
Salmonella Infections ◽  
Salmonella Pullorum ◽  
Somatic Antigens ◽  
Highly Virulent

Salmonella enteritidis is highly virulent for the mouse causing an infection resembling mouse typhoid. Survivors of the infection are completely resistant to reinfection and eliminate a large challenge dose of virulent organisms within 72 hr. The antigenically related Salmonella gallinarum was almost avirulent for the mouse but animals vaccinated with this organism were equally capable of eliminating a lethal dose of virulent S. enteritidis. Living Salmonella pullorum, on the other hand, was quickly eliminated from the tissues of normal mice. Vaccination with this organism failed to evoke an effective bactericidal mechanism. Alcohol-killed vaccines of these three Salmonellae all produced an increase in blood clearance rate, but gave only marginal protection against S. enteritidis. Liver and spleen counts on these mice revealed a 1 to 2 day delay before any net increase in the total bacterial population could be observed. Immunization of mice with increasing doses of living Salmonella montevideo resulted in progressively greater killing of a challenge dose of S. enteritidis despite the absence of common somatic antigens between the two strains. The degree of protection varied with the size of the residual population of S. montevideo in the vaccinated mice. The significance of these findings in assessing the importance of various factors involved in the development of acquired resistance to Salmonella infections is discussed.

scholarly journals In vitro tracheospasmolytic effect and acute toxicity screening of Coptosapelta flavescens Korth root ’s water extract

2020 ◽  
Vol 11 (SPL4) ◽  
pp. 949-954
Author(s):  
Khemasili Kosala ◽  
Sjarif Ismail ◽  
Ika Fikriah ◽  
Yovita Gunawan
Keyword(s):  
Daphnia Magna ◽  
Adrenergic Receptors ◽  
Lethal Dose ◽  
Water Extract ◽  
Relaxation Mechanism ◽  
Tracheal Ring ◽  
Artemia Salina ◽  
Toxicity Screening ◽  
The Right

There are no data available regarding the bronchospasmolytic activity and toxicity of water extract of Coptosapelta flavescens Korth root (WECFR). Therefore, this study aimed to determine: a. the in vitro tracheospasmolytic effect of WECFR; b. safety of WECFR using the brine shrimp lethality test (BSLT) and immobilization of Daphnia magna larvae (IDL). In study, a guinea pig tracheal ring was contracted with methacholine and cumulative doses of WECFR solution were administered. A dose-response curve (DRC) was plotted of the percentage of the tracheal ring relaxation response. To test whether the relaxation mechanism occured through stimulation of beta2-adrenergic receptors, the tracheal ring was incubated with propranolol. Data analyzed using analysis of variance, showed that the DRC of WECFR was obtained with p < 0.05 compared to the DRC of control, indicating that WECFR had a tracheospasmolytic effect. The DRC for propranolol-blocked WECFR did not shift to the right compared to the DRC of WECFR, confirming that the relaxation mechanism did not occur through the beta2-adrenergic receptors. Study b. assessed safety using BSLT and IDL. After exposing the larvae to WECFR and control for 24 and 48 h, respectively, the number of dead larvae was counted. Data analyzed using Probit program, showed that the lethal dose 50 of WECFR towards Artemia salina and Daphnia magna larvae was > 1000 ppm, which means that it was not toxic. This studies demonstrate that WECFR exhibits tracheospasmolitic effect, but not through beta2-adrenergic receptors; WECFR is safe for Artemia salina and Daphnia magna larvae.

scholarly journals A broadly neutralizing biparatopic Nanobody protects mice from lethal challenge with SARS-CoV-2 variants of concern

2021 ◽  
Author(s):  
Teresa R. Wagner ◽  
Daniel Schnepf ◽  
Julius Beer ◽  
Karin Klingel ◽  
Natalia Ruetalo ◽  
...  
Keyword(s):  
Lethal Dose ◽  
Survival Rates ◽  
Drug Candidate ◽  
Lethal Challenge ◽  
Drug Candidates ◽  
High Affinity ◽  
Neutralizing Capacity ◽  
Future Drug

The ongoing COVID-19 pandemic and the frequent emergence of new SARS-CoV-2 variants of concern (VOCs), requires continued development of fast and effective therapeutics. Recently, we identified high-affinity neutralizing nanobodies (Nb) specific for the receptor-binding domain (RBD) of SARS-CoV-2, which are now being used as biparatopic Nbs (bipNbs) to investigate their potential as future drug candidates. Following detailed in vitro characterization, we chose NM1267 as the most promising candidate showing high affinity binding to several recently described SARS-CoV-2 VOCs and strong neutralizing capacity against a patient isolate of B.1.351 (Beta). To assess if bipNb NM1267 confers protection against SARS-CoV-2 infection in vivo, human ACE2 transgenic mice were treated by intranasal route before infection with a lethal dose of SARS-CoV-2. NM1267-treated mice showed significantly reduced disease progression, increased survival rates and secreted less infectious virus via their nostrils. Histopathological analyses and in situ hybridization further revealed a drastically reduced viral load and inflammatory response in lungs of NM1267-treated mice. These data suggest, that bipNb NM1267 is a broadly active and easily applicable drug candidate against a variety of emerging SARS-CoV-2 VOCs.

scholarly journals 1231. VIR-2482: A potent and broadly neutralizing antibody for the prophylaxis of influenza A illness

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S635-S636
Author(s):  
Matteo Samuele Pizzuto ◽  
Fabrizia Zatta ◽  
Andrea Minola ◽  
Alessia Peter ◽  
Katja Culap ◽  
...  
Keyword(s):  
Half Life ◽  
Influenza A ◽  
Lethal Dose ◽  
A549 Cells ◽  
Neutralizing Antibody ◽  
Life Extension ◽  
Influenza A Viruses ◽  
Head Region ◽  
Lethal Challenge

Abstract Background Influenza A viruses are responsible for seasonal epidemics and represent a constant pandemic threat. Influenza vaccines induce predominantly antibodies against the head region of hemagglutinin (HA) and are strain specific. Vaccine effectiveness is often suboptimal due to mismatch with drifting viruses and an inadequate immune response. Broadly neutralizing monoclonal antibodies (mAbs) targeting the conserved stem-region of HA may provide protection through multiple seasons and cover strains with pandemic potential. We report pre-clinical data on VIR-2482, a fully human anti-HA stem mAb with half-life extending Fc mutations. Methods Binding of VIR-2482 to a panel of influenza HAs and neutralization of H1N1 and H3N2 viruses were measured by ELISA and microneutralization. Epitope conservation was evaluated using 49,462 HA sequences retrieved from GiSAID. Engagement of human FcγRs by VIR-2482 was assessed by biolayer interferometry. Antibody-dependendent cell-mediated cytoxicity (ADCC) was measured via in vitro killing of A549 cells expressing H1-HA glycoprotein by human NK cells. Complement-dependent cytotoxicity (CDC) was evaluated by incubating VIR-2482 with H1N1 infected cells in the presence of guinea pig complement. Protection studies were performed in Balb/c mice given VIR-2482 24h before intranasal infection with a lethal dose of H1N1 PR8 and H3N2 HK/68. Results VIR-2482 binds to the HA proteins representing all 18 influenza A HA subtypes and neutralizes a broad panel of H1N1 and H3N2 viruses spanning almost 100 years of evolution. Bioinformatic analysis revealed &gt;98.8% conservation for the majority of key contact residues examined from sequences retrieved for H1N1 and H3N2 between 2009-2019. The half-life extending mutations in the Fc portion do not affect the ability of the antibody to engage FcγRIIIa, FcγRIIa, and C1q as evidenced by their lack of impact on ADCC and CDC in vitro. Prophylactic administration of VIR-2482 protects Balb/c mice from infection with lethal challenge doses of H1N1 and H3N2 viruses. Conclusion The attributes of potency, broad recognition of a highly conserved epitope, retention of high-level effector functions in addition to half-life extension support the development of VIR-2482 as a universal prophylactic for influenza A illness. Disclosures Matteo Samuele Pizzuto, PhD, VIR Biotechnology (Employee) Fabrizia Zatta, n/a, Vir Biotechnology (Employee) Andrea Minola, MS, Vir Biotechnology (Employee) Alessia Peter, n/a, Vir Biotechnology (Employee) Katja Culap, n/a, Vir Biotechnology (Employee) Leah Soriaga, PhD, Vir Biotechnology (Employee) Anna De Marco, n/a, Vir Biotechnology (Employee) Barbara Guarino, PhD, Vir Biotechnology (Employee) Nadia Passini, n/a, Vir Biotechnology (Employee) David K. Hong, MD, Vir Biotechnology (Employee) Fabio Benigni, PhD, Vir Biotechnology (Employee) Christy Hebner, PhD, Vir Biotechnology (Employee) Aurelio Bonavia, PhD, Vir Biotechnology (Employee) Davide Corti, PhD, Vir Biotechnology (Employee)

scholarly journals Efficacy of Oritavancin in a Murine Model of Bacillus anthracis Spore Inhalation Anthrax

2008 ◽  
Vol 52 (9) ◽  
pp. 3350-3357 ◽  
Author(s):  
H. S. Heine ◽  
J. Bassett ◽  
L. Miller ◽  
A. Bassett ◽  
B. E. Ivins ◽  
...  
Keyword(s):  
Bacillus Anthracis ◽  
Lethal Dose ◽  
Standard Of Care ◽  
Significant Activity ◽  
Postexposure Prophylaxis ◽  
Current Standard ◽  
Lethal Challenge ◽  
Inhalation Anthrax ◽  
Ames Strain

ABSTRACT The inhaled form of Bacillus anthracis infection may be fatal to humans. The current standard of care for inhalational anthrax postexposure prophylaxis is ciprofloxacin therapy twice daily for 60 days. The potent in vitro activity of oritavancin, a semisynthetic lipoglycopeptide, against B. anthracis (MIC against Ames strain, 0.015 μg/ml) prompted us to test its efficacy in a mouse aerosol-anthrax model. In postexposure prophylaxis dose-ranging studies, a single intravenous (i.v.) dose of oritavancin of 5, 15, or 50 mg/kg 24 h after a challenge with 50 to 75 times the median lethal dose of Ames strain spores provided 40, 70, and 100% proportional survival, respectively, at 30 days postchallenge. Untreated animals died within 4 days of challenge, whereas 90% of control animals receiving ciprofloxacin at 30 mg/kg intraperitoneally twice daily for 14 days starting 24 h after challenge survived. Oritavancin demonstrated significant activity post symptom development; a single i.v. dose of 50 mg/kg administered 42 h after challenge provided 56% proportional survival at 30 days. In a preexposure prophylaxis study, a single i.v. oritavancin dose of 50 mg/kg administered 1, 7, 14, or 28 days before lethal challenge protected 90, 100, 100, and 20% of mice at 30 days; mice treated with ciprofloxacin 24 h or 24 and 12 h before challenge all died within 5 days. Efficacy in pre- and postexposure models of inhalation anthrax, together with a demonstrated low propensity to engender resistance, promotes further study of oritavancin pharmacokinetics and efficacy in nonhuman primate models.

scholarly journals Protection from lethal challenge in a neonatal mouse model by circulating recombinant form coxsackievirus A16 vaccine candidates

2014 ◽  
Vol 95 (5) ◽  
pp. 1083-1093 ◽  
Author(s):  
Jingliang Li ◽  
Junliang Chang ◽  
Xin Liu ◽  
Jiaxin Yang ◽  
Haoran Guo ◽  
...  
Keyword(s):  
Mouse Model ◽  
Vaccine Development ◽  
Lethal Dose ◽  
Neonatal Mouse ◽  
Recombinant Form ◽  
Control Group ◽  
Coxsackievirus A16 ◽  
Lethal Challenge ◽  
Vaccine Candidates

Circulating coxsackievirus A16 (CA16) is a major cause of hand, foot and mouth disease (HFMD) in South-east Asia. At present, there is no vaccine against CA16. Pathogenic animal models that are sensitive to diverse circulating CA16 viruses would be desirable for vaccine development and evaluation. In this study, we isolated and characterized several circulating CA16 viruses from recent HFMD patients. These CA16 viruses currently circulating in humans were highly pathogenic in a newly developed neonatal mouse model; we also observed and analysed the pathogenesis of representative circulating recombinant form CA16 viruses. An inactivated CA16 vaccine candidate, formulated with alum adjuvant and containing submicrogram quantities of viral proteins, protected neonatal mice born to immunized female mice from lethal-dose challenge with a series of CA16 viruses. Further analysis of humoral immunity showed that antibody elicited from both the immunized dams and their pups could neutralize various lethal viruses by a cytopathic effect in vitro. Moreover, viral titres and loads in the tissues of challenged pups in the vaccine group were far lower than those in the control group, and some were undetectable. This lethal-challenge model using pathogenic CA16 viruses and the vaccine candidates that mediated protection in this model could be useful tools for the future development and evaluation of CA16 vaccines.

scholarly journals A Recombinant Live Attenuated Strain of Vibrio cholerae Induces Immunity against Tetanus Toxin andBordetella pertussis Tracheal Colonization Factor

1998 ◽  
Vol 66 (4) ◽  
pp. 1648-1653 ◽  
Author(s):  
Inês Chen ◽  
Theresa M. Finn ◽  
Liu Yanqing ◽  
Qi Guoming ◽  
Rino Rappuoli ◽  
...  
Keyword(s):  
Vibrio Cholerae ◽  
Tetanus Toxin ◽  
Bacterial Colonization ◽  
Lethal Dose ◽  
Lethal Challenge ◽  
Colonization Factor ◽  
Heterologous Antigens

ABSTRACT An attenuated strain of Vibrio cholerae was used as a carrier for the expression of heterologous antigens such as fragment C from tetanus toxin (TetC) and tracheal colonization factor fromBordetella pertussis (Tcf). In vitro, high levels of protein were obtained when the Escherichia coli nirBpromoter was used and the bacteria were grown with low aeration. Intranasal immunization of mice with IEM101 expressing TetC elicited serum vibriocidal activity and induced antibodies against tetanus toxin which were protective against lethal challenge with 10 times the 50% lethal dose of tetanus toxin. Bacterial viability was essential for the induction of anti-TetC antibodies. Intranasal administration of IEM101 expressing Tcf induced a significant reduction in bacterial colonization of the tracheas of mice challenged with wild-type B. pertussis. These data are in agreement with the putative role of Tcf in Bordetellatracheal colonization. In conclusion, we have demonstrated thatV. cholerae may be used as a live vector to deliver heterologous antigens in vivo and that protection to both systemic and local challenge may be achieved.

Inhibitory effects of epimedium herb water extract on the inflammatory response in vitro and in vivo

Planta Medica ◽  
2016 ◽  
Vol 81 (S 01) ◽  
pp. S1-S381
Author(s):  
YC Oh ◽  
YH Jeong ◽  
WK Cho ◽  
SJ Lee ◽  
JY Ma
Keyword(s):  
Inflammatory Response ◽  
Water Extract ◽  
Inhibitory Effects

Hepato- and Nephroprotective Effects of the Polyphenol Concentrate From Cabernet Sauvignon Grape Varieties Cultivated in Kazakhstan in the Experimental Model Of CCL4-Induced Toxicity

2017 ◽  
Vol 9 (03) ◽  
Author(s):  
Nurgozhin T. ◽  
Sergazy S. H. ◽  
Adilgozhina G. ◽  
Gulyayev A. ◽  
Shulgau Z. ◽  
...  
Keyword(s):  
Carbon Tetrachloride ◽  
Experimental Model ◽  
Lethal Dose ◽  
Radical Scavenging ◽  
Cabernet Sauvignon ◽  
Intragastric Administration ◽  
Liver And Kidney ◽  
Antioxidant Stress

Objective:This study investigates the hepatoprotective effect and the antioxidant role of polyphenol concentrate in the experimental model of carbon tetrachloride (CCl4) induced toxicity. Methods: Antioxidant activity of Cabernet Sauvignon grape polyphenol were evaluated by radical scavenging of 1,1-diphenyl-2-picryl hydrazyl radical (DPPH), 2,2’-azinobis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS.+). In addition, the effects of polyphenol concentrate on the survival of Wistar rats in the toxicity model, was also investigated. The polyphenol concentrate was administered for 5 five days prior to injection of carbon tetrachloride in a sub-lethal dose of 300 mg/kg of animal body weight in order to perform histological examinations of the liver and kidney, and detect the levels of AST, ALT and bilirubin. Results: Administration of polyphenol concentrate increased animal survival in the experimental model. Moreover, the intragastric administration of polyphenol concentrate prior to the initiation of the experimental model of toxicity, which was caused by a sub-lethal CCl4 dose, reduced morphological injuries in the liver and kidney, decreased the AST and ALT levels of the blood serum. Discussion and conclusion: Our data demonstrate that polyphenol concentrate possesses an antioxidant potential both in vitro and in vivo by reducing antioxidant stress that was caused by CCl4 administration into rats.

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