Chagas cardiomyopathy is caused by
(
). Two antigenic candidates, TcG2 and TcG4, are recognized by antibodies in naturally infected dogs and humans; and these vaccine candidates provided protection ...from
infection in mice and dogs.
(
) is non-pathogenic to mammals and shown to elicit cross-reactive anti-
antibodies. In this study, we investigated if fixed
(fTr) can further enhance the efficacy of the
DNA vaccine.
C57BL/6 mice were immunized with
DNA vaccine and fTr (delivered as an adjuvant or in prime-boost approach), and challenged with
. Serology studies showed that fTr (±quil-A) elicited
- and
reactive IgGs that otherwise were not stimulated by
vaccine only, and quil-A had suppressive effects on fTr-induced IgGs. After challenge infection,
-vaccinated mice exhibited potent expansion of antigen- and
-specific IgGs that were not boosted by fTr±quil-A. Flow cytometry analysis showed that
-induced dendritic cells (DC) and macrophages (Mφ) responded to challenge infection by expression of markers of antigen uptake, processing, and presentation, and production of pro-inflammatory cytokines.
-induced CD4
T cells acquired Th1 phenotype and expressed markers that orchestrate adaptive immunity. A fraction of vaccine-induced CD4
T cells exhibited iTreg phenotype responsible for aversion of self-injurious immune responses. Further,
-vaccinated mice exhibited potent expansion of poly-functional CD8
T cells with TNF-α/IFN-γ production and cytolytic phenotype post-infection. Subsequently, tissue parasites and pathology were hardly detectable in
-vaccinated/infected mice. Inclusion of fTr±quil-A had no clear additive effects in improving the
-specific adaptive immunity and parasite control than was noted in mice vaccinated with
alone. Non-vaccinated mice lacked sufficient activation of Th1 CD4
/CD8
T cells, and exhibited >10-fold higher levels of tissue parasite burden than was noted in vaccinated/infected mice.
vaccine elicits highly effective immunity, and inclusion of fTr is not required to improve the efficacy of DNA vaccine against acute
infection in mice.
Mapping B and T cell epitopes constitutes an important action for peptide vaccine design. PLD and CP40 virulence factors of
biovar
, a causal agent of Caseous Lymphadenitis, have been evaluated in a ...murine model as good candidates for vaccine development. Therefore, the goal of this work was to in silico analyze B and T cell epitopes of the PLD and CP40 proteins of a Mexican isolate of
. The Immune Epitope Data Base and Resource website was employed to predict the linear and conformational B-cell, T CD4+, and T CD8+ epitopes of PLD and CP40 proteins of
Mexican strain 2J-L. Fifty B cell epitopes for PLD 2J-L and forty-seven for CP40 2J-L were estimated. In addition, T CD4+ and CD8+ cell epitopes were predicted for PLD 2J-L (MHC I:16 epitopes, MHC II:10 epitopes) and CP40 2J-L (MHC I: 15 epitopes, MHC II: 13 epitopes). This study provides epitopes, paying particular attention to sequences selected by different predictor programs and overlap sequences as B and T cell epitopes. PLD 2J-L and CP40 2J-L protein epitopes may aid in the design of a promising peptide-based vaccine against Caseous Lymphadenitis in Mexico.
ChEMBL biological activities prediction for 1–5-bromofur-2-il-2-bromo-2-nitroethene (G1) is a difficult task for cytokine immunotoxicity. The current study presents experimental results for G1 ...interaction with mouse Th1/Th2 and pro-inflammatory cytokines using a cytometry bead array (CBA). In the in vitro test of CBA, the results show no significant differences between the mean values of the Th1/Th2 cytokines for the samples treated with G1 with respect to the negative control, but there are moderate differences for cytokine values between different periods (24/48 h). The experiments show no significant differences between the mean values of the pro-inflammatory cytokines for the samples treated with G1, regarding the negative control, except for the values of tumor necrosis factor (TNF) and Interleukin (IL6) between the group treated with G1 and the negative control at 48 h. Differences occur for these cytokines in the periods (24/48 h). The study confirmed that the antimicrobial G1 did not alter the Th1/Th2 cytokines concentration in vitro in different periods, but it can alter TNF and IL6. G1 promotes free radicals production and activates damage processes in macrophages culture. In order to predict all ChEMBL activities for drugs in other experimental conditions, a ChEMBL data set was constructed using 25 biological activities, 1366 assays, 2 assay types, 4 assay organisms, 2 organisms, and 12 cytokine targets. Molecular descriptors calculated with Rcpi and 15 machine learning methods were used to find the best model able to predict if a drug could be active or not against a specific cytokine, in specific experimental conditions. The best model is based on 120 selected molecular descriptors and a deep neural network with area under the curve of the receiver operating characteristic of 0.904 and accuracy of 0.832. This model predicted 1384 G1 biological activities against cytokines in all ChEMBL data set experimental conditions.
The emergence of reduced susceptibility to fluoroquinolones among Salmonella enterica serotype Typhimurium isolates leading to clinical failure of treatment poses a great therapeutic challenge.
The ...current study is focused on the evaluation of the minimum inhibitory concentration (MIC) of quinolones in 29 Salmonella typhimurium of 86 Salmonella spp. strains, obtained from pigs from the State of Mexico. The MIC was performed with the Kirby-Bauer method. On the other hand, the GyrA gene was sequenced. The present study was undertaken to describe the resistance profiles and fluoroquinolone resistance mechanism of Salmonella Typhimurium.
The DNA sequence of the gyrA genes from Salmonella enterica serovar typhimurium revealed strong similarity between gyrA and its counterpart in Escherichia coli. The sequencing of quinolone resistance-determining region (QRDR) of the gyrA gene showed the presence of mutation at either S83 or at D87 in almost all the Salmonella typhimurium isolates.
This mutation, although phenotypically expressed as decreased susceptibility to fluoroquinolones goes undetected by the disk diffusion method using the present method of Kirby-Bauer. Hence, it can increase morbidity and mortality due to delay in appropriate antibiotic treatment.
Peptides constitute an alternative and interesting option to develop treatments, vaccines, and diagnostic tools as they demonstrate their scope in several health aspects; as proof of this, commercial ...peptides for humans and animals are available on the market and used daily. This review aimed to know the role of peptides in the field of veterinary diagnosis, and include peptide-based enzyme-linked immunosorbent assay (pELISA), lateral flow devices, and peptide latex agglutination tests that have been developed to detect several pathogens including viruses and bacteria of health and production relevance in domestic animals. Studies in cattle, small ruminants, dogs, cats, poultry, horses, and even aquatic organisms were reviewed. Different studies showed good levels of sensitivity and specificity against their target, moreover, comparisons with commercial kits and official tests were performed which allowed appraising their performance. Chemical synthesis, recombinant DNA technology, and enzymatic synthesis were reviewed as well as their advantages and drawbacks. In addition, we discussed the intrinsic limitations such as the small size or affinity to polystyrene membrane and mention several strategies to overcome these problems. The use of peptides will increase in the coming years and their utility for diagnostic purposes in animals must be evaluated.
Acute phase proteins have been used as tools for the diagnosis, monitoring, and prognosis of several diseases in domestic animals. However, the dynamics of these proteins in infection by 'Trypanosoma ...cruzi', the causative agent of Chagas disease in dogs, is still unknown. The aim of this study was to determine concentrations of acute phase proteins (C-reactive protein, haptoglobin, ferritin and paraoxonase-1) in dogs in a coastal town of Ecuador, with natural 'Trypanosoma cruzi' infection with or without seroreactivity of 'Ehrlichia canis', 'Ehrlichia ewingii', 'Anaplasma phagocytophilum', 'Anaplasma platys', 'Borrelia burgdorferi' and 'Dirofilaria immitis'. For the detection of 'Trypanosoma cruzi' serum antibodies, two different antigen-based enzyme-linked immunosorbent assay tests were implemented. For the detection of seroreactivity of 'Ehrlichia canis', 'Ehrlichia ewingii', 'Anaplasma phagocytophilum', 'Anaplasma platys', 'Borrelia burgdorferi' and 'Dirofilaria immitis', an IDEXX SNAP 4Dx test was used. To determine the concentration of C-reactive protein and ferritin, an immunoturbidimetric assay was used; haptoglobin concentration was measured using a commercial colorimetric method validated in dogs; a spectrophotometric method was used to determine the serum concentration of paraoxonase-1. Results showed a reduction in the serum levels of paraoxonase-1 in 'Trypanosoma cruzi'-seroreactive dogs, either with or without seroreactivity to other vector-borne diseases. A serum ferritin increment was observed in 'Trypanosoma cruzi'-seroreactive dogs with seroreactivity to any other vector-borne diseases. Our findings suggest that paraoxonase-1 levels are reduced in 'Trypanosoma cruzi'-seroreactive dogs without evident clinical signs of Chagas disease, despite their seroreactivity to the other vector-borne diseases studied. These findings could indicate an oxidative stress response in 'Trypanosoma cruzi'-seroreactive dogs with no evident signs of inflammation.
The global antibacterial resistance requires urgent attention from different fields of engineering. Here, several unit operations were assessed in a novel water treatment train capable of remediating ...antibacterials, metals and pathogenic DNA to generate clean water. The analyses used 14C-respirometry, spectrometry, and a set of molecular analyses. Multiresistant bacteria hold antibacterial resistance genes (ARGs), which were harnessed for bioremediation of pollutant mixtures. Treatment efficiencies were 25–71% for 8-days with aerobic Cr(VI) reduction and removal of Cd and Pb; and 34.8% erythromycin (ERY) was biodegraded aerobically in 20 days. The anaerobic digestion (AD) bioremediated 65–73% mixed antibacterials ERY and sulfamethoxazol (SMX) in 60 days. However, high concentrations of mixed antibacterials induced inhibition of bacteria and methanogens and higher diversity of ARGs. ARGs were eliminated at 60 °C and 5.8 kPa for 10 min. The suggested coupling sequence of operations was metal, then antibacterial aerobic bioremediation, AD (yielding biomethane as energy source), recirculation of ARGs in situ, and thermo-pressure pathogenic DNA degradation.
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•A complete treatment train dealing with resistance genes is discussed for the first time.•Molecular and genetic analysis done to pinpoint parameters of the treatment train.•Interactions among antibiotics and metals were studied.•Antibacterial resistance genes must be treated in situ to avoid dispersion.
Trypanosoma cruzi (T. cruzi) is the causative agent for Chagas disease (CD). There is a critical lack of methods for prevention of infection or treatment of acute infection and chronic disease. ...Studies in experimental models have suggested that the protective immunity against T. cruzi infection requires the elicitation of Th1 cytokines, lytic antibodies and the concerted activities of macrophages, T helper cells, and cytotoxic T lymphocytes (CTLs). In this review, we summarize the research efforts in vaccine development to date and the challenges faced in achieving an efficient prophylactic or therapeutic vaccine against human CD.
Pathogenesis of Chagas disease (CD) caused by
involves chronic oxidative and inflammatory stress. In this review, we discuss the research efforts in therapeutic vaccine development to date and the ...potential challenges imposed by oxidative stress in achieving an efficient therapeutic vaccine against CD.
This review covers the immune and nonimmune mechanisms of reactive oxygen species production and immune response patterns during
in CD. A discussion on immunotherapy development efforts, the efficacy of antigen-based immune therapies against
, and the role of antioxidants as adjuvants is discussed to provide promising insights to developing future treatment strategies against CD.
Administration of therapeutic vaccines can be a good option to confront persistent parasitemia in CD by achieving a rapid, short-lived stimulation of type 1 cell-mediated immunity. At the same time, adjunct therapies could play a critical role in the preservation of mitochondrial metabolism and cardiac muscle contractility in CD. We propose combined therapy with antigen-based vaccine and small molecules to control the pathological oxidative insult would be effective in the conservation of cardiac structure and function in CD.
Objetivo. Realizar el aislamiento del virus de la viremia primaveral de la carpa (SVCV) en ejemplares de carpa común (Cyprinus carpió), evaluar su crecimiento en diferentes tipos de células, así como ...la supervivencia viral a diferentes temperaturas. Materiales y métodos. Diez carpas de entre 400-500 gramos de una laguna del centro de México fueron procesadas para el diagnóstico de SVCV mediante aislamiento en cultivo de células y RT-PCR semianidado. El virus obtenido se inoculó en células EPC, BF-2, CHSE-214 y RTG-2 para determinar diferencias de crecimiento de SVCV. Además, se evaluó la supervivencia del virus conservado a temperatura ambiente (TA 20-25gradosC), refrigeración (REF 4gradosC) y congelación (CONG -80gradosC) hasta once meses. Los órganos internos se procesaron para análisis histológico. Resultados. Los peces analizados no presentaron signos externos sugestivos de enfermedad, pero interna e histopatológicamente se observaron lesiones sugestivas de infección sistémica. SVCV fue aislado en células EPC y BF-2 y confirmado por RT-PCR semianidado. SVCV únicamente indujo CPE en células EPC y BF-2 y fue negativo en RTG-2 y CHSE-214. El virus conservado a TA perdió viabilidad después de cuatro meses post infección (mpi), siendo total a seis mpi; mientras REF y CONG fueron estables durante los once meses de estudio. Conclusiones. La infección subclínica por SVCV fue confirmada en carpas que presentaron lesiones histológicas asociadas a esta infección. SVCV únicamente causó CPE en células EPC y BF-2 y el virus conservó su viabilidad a 4gradosC y -80gradosC hasta once meses; mientras que a TA se perdió en seis meses. Palabras clave: Cyprinus carpió; peces; enfermedad; RT-PCR; infección, células (Fuente: AGROVOQ. Objective. To perform the isolation of spring viremia of carp virus (SVCV) in common carp (Cyprinus carpió) and evaluate its growth in different cell types and viral survival at different temperatures. Materials and methods. Ten carps of between 400-500 grams of a lagoon in central Mexico were processed for diagnosis of SVCV by isolation in cell culture and by RT-PCR. The virus obtained was inoculated into EPC, BF-2, CHSE-214 and RTG-2 cells to determine differences in virus growth; the survival of virus stored at room temperature (TA 20-25gradosC), refrigeration (REF 4gradosC) and freezing (CONG -80gradosC) up to eleven months was also evaluated. Internal organ samples were processed for histological analysis. Results. The fish analyzed did not show external signs suggestive of disease but internally and histopathologically lesions suggestive of systemic infection were observed. SVCV was isolated in EPC and BF-2 cells and confirmed by semi-nested RT-PCR. SVCV only induced CPE in EPC and BF-2 cells and was negative in RTG-2 and CHSE-214. The virus conserved at TA lost viability after four months post-infection (mpi), being total at six mpi; while REF and CONG were stable during the eleven months. Conclusions. Subclinical SVCV infection was confirmed in carp that presented histological lesions associated with this infection; SVCV only caused CPE in EPC and BF-2 cells; and the virus kept in refrigeration and at -80gradosC retained its viability up to eleven months; while TA was lost in six months. Keywords: Cyprinus carpió; fish; disease; RT-PCR; infection; cells (Source: AGROVOC).
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