ABSTRACT
Abstract The cattle tick Rhipicephalus microplus causes significant economic losses in agribusiness. Control of this tick is achieved mainly through the application of chemical acaricides, often resulting in contamination of animal food products and of the environment. Another major concern associated with acaricide use is the increasing reports of resistance of this tick vector against the active ingredients of many commercial products. An alternative control method is vaccination. However, the commercially available vaccine based on a protein homologous to Bm86 exhibits variations in efficacy relative to the different geographical locations. This study aimed to identify antigenic determinants of the sequences of proteins homologous to Bm86. Phylogenetic analyses were performed to determine the extent of divergence between different populations of R. microplus to identify the sequence that could be used as a universal vaccine against the multiple geographically distinct populations of R. microplus and related tick species. Considering the extensive sequence and functional polymorphism observed among strains of R. microplus from different geographical regions, we can conclude that it may be possible to achieve effective vaccination against these cattle ticks using a single universal Bm86-based antigen.
Resumo O carrapato Rhipicephalus microplus é responsável por perdas significativas no agronegócio. O controle deste carrapato é feito principalmente por meio da aplicação de acaricidas químicos, geralmente resultando na contaminação de produtos de origem animal e do meio ambiente. Outra preocupação importante associada ao uso de acaricidas é o crescente aumento de relatos sobre a resistência deste carrapato a princípios ativos de vários produtos comerciais. Uma alternativa de controle é por meio de vacinação. Porém, a vacina comercializada contendo proteína homóloga à Bm86, apresenta variações de eficácia em relação às diferentes localizações geográficas. Este estudo buscou identificar determinantes antigênicos das sequencias de proteínas homólogas a Bm86. As análises filogenéticas foram feitas para determinar a extensão da divergência entre diferentes populações de R. microplus com o objetivo de identificar a sequência que poderia ser usada como vacina universal contra as múltiplas populações geograficamente distintas de R. microplus e espécies de carrapatos relacionados. Considerando-se a extensa sequência e o polimorfismo observados entre linhagens de R. microplus de diferentes regiões geográficas, podemos concluir que pode ser possível obter uma vacinação efetiva contra esses carrapatos bovinos utilizando um único antígeno universal baseado em Bm86.
Subject(s)
Animals , Cattle , Tick Infestations/prevention & control , Vaccines/chemistry , Proteins/immunology , Cattle Diseases/prevention & control , Rhipicephalus/immunology , Epitopes/immunology , Vaccines/administration & dosageABSTRACT
Objective The aim of this study was to evaluate the genetic expression of adipokines in the adipocytes of monosodium glutamate (MSG)-treated obese rats submitted to physical activity.Materials and methods Obesity was induced by neonatal MSG administration. Exercised rats (MSG and control) were subjected to swim training for 30 min for 10 weeks, whereas their respective controls remained sedentary. Total RNA was obtained from sections of the mesenteric adipose tissue of the rats. mRNA levels of adiponectin (Adipoq), tumor necrosis factor alpha (Tnf), peroxisome proliferator-activated receptor alpha (Ppara), and peroxisome proliferator-activated receptor gamma (Pparg) adipokines were quantified by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR).Results In the exercise-trained control group, the expression of Adipoq increased compared to the sedentary control, which was not observed in the MSG-obese rats. Increased levels of Tnf in MSG-obese rats were not reversed by the swim training. The expression of Ppara was higher in sedentary MSG-obese rats compared to the sedentary control. Swimming increased this adipokine expression in the exercise-trained control rats compared to the sedentary ones. mRNA levels of Pparg were higher in the sedentary MSG-rats compared to the sedentary control; however, the exercise did not influenced its expression in the groups analyzed.Conclusions In conclusion, regular physical activity was not capable to correct the expression of proinflammatory adipokines in MSG-obese rat adipocytes.
Subject(s)
Animals , Humans , Adjuvants, Immunologic , Molecular Mimicry/immunology , Tumor Necrosis Factors , Vaccines, Synthetic/immunology , Vaccines/chemistry , Vaccines/immunology , Adjuvants, Immunologic/chemistry , /immunology , /chemistry , /metabolism , Cancer Vaccines/chemistry , Cancer Vaccines/immunology , Genetic Vectors/genetics , Genetic Vectors/immunology , Immunotherapy , Ligands , Lentivirus/genetics , Lentivirus/immunology , Macaca mulatta , Neoplasms/immunology , Neoplasms/therapy , Protein Multimerization , TNF-Related Apoptosis-Inducing Ligand/chemistry , Toll-Like Receptors/agonists , Tumor Necrosis Factors/chemistry , Vaccines, Synthetic/chemistry , Viral Matrix Proteins/immunologyABSTRACT
Aluminum salts have been widely used in vaccine formulations and, after their introduction more than 80 years ago, only few vaccine formulations using new adjuvants were developed in the last two decades. Recent advances in the understanding of how innate mechanisms influence the adaptive immunity opened up the possibility for the development of new adjuvants in a more rational design. The purpose of this review is to discuss the recent advances in this field regarding the attempts to determine the molecular basis and the general mechanisms underlying the development of new adjuvants, with particular emphasis on the activation of receptors of innate immune recognition. One can anticipate that the use of these novel adjuvants will also provide a window of opportunities for the development of new vaccines.
Subject(s)
Animals , Humans , Adaptive Immunity/immunology , Immunity, Innate/immunology , Receptors, Pattern Recognition/immunology , Vaccines/immunology , Virulence Factors/immunology , Adjuvants, Immunologic/chemistry , Aluminum Compounds/immunology , Immunity, Cellular/immunology , Pertussis Vaccine/immunology , Toll-Like Receptors/immunology , Vaccines, Attenuated/immunology , Vaccines/chemistryABSTRACT
El timerosal es un derivado del mercurio utilizado desde 1930 como preservante de vacunas. En las últimas décadas ha sido cuestionada su seguridad, especialmente por la posibilidad de toxicidad neurológica. La revisión de varios estudios realizados en niños que recibieron vacunas que contienen timerosal y la posición de organismos de expertos internacionales en relación al uso de este compuesto en vacunas, permite al Comité Consultivo de Inmunizaciones concluir que no existe evidencia de eventos adversos en lactantes o niños por exposición al timerosal contenido en vacunas rutinarias y, por lo tanto, no habría razón para modificar las actuales prácticas de inmunización en Chile.
Thimerosal is a mercury derivative included in vaccines since 1930 with the aim to prevent microbial contamination. During the last decades, the use of thimerosal has been questioned, specifically because of a potential association with neurotoxicity. After a thorough review of published studies on pediatric use of thimerosal-containing vaccines, and of position papers from international expert groups, the Consultive Committee of Immunizations of the Chilean Society of Infectious Diseases concludes that there is no solid evidence of adverse events associated with the use of thimerosal containing vaccines in infants and children. Therefore, a change in current vaccine practices refererred to thimerosal-containing vaccines is not justified in Chile.
Subject(s)
Child , Humans , Infant , Preservatives, Pharmaceutical , Thimerosal , Vaccines/chemistry , Autistic Disorder/chemically induced , Chile , Preservatives, Pharmaceutical/adverse effects , Reference Standards , Societies, Medical , Thimerosal/adverse effects , Vaccines/adverse effectsABSTRACT
Dendritic cells play an important role in the development of effective cancer vaccines. These cells have the potential to present tumour-specific antigens and thereby induce an immune response. Various studies involving clinical trials have investigated the efficacy of administering antigen-loaded dendritic cells for cancer therapy. In order to design such experiments it is important to consider specific antigens, which initiate either a CD4+ or CD8+ response or both. The present review discusses the unique properties of dendritic cells as an immunotherapeutic cell for cancer.
Subject(s)
Antigens, Neoplasm/chemistry , CD4-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/metabolism , Clinical Trials as Topic , Dendritic Cells/cytology , Humans , Immunotherapy/methods , Neoplasms/therapy , Peptides/chemistry , Transfection , Vaccines/chemistrySubject(s)
Drug Stability , Drug Storage/methods , Equipment Design , Humans , India , Refrigeration , Temperature , Vaccines/chemistryABSTRACT
Autoclaved cercarial vaccine (ACV) was found to be highly effective in eliciting protective immunity against experimental Schistosomal mansoni. So, the aim of this study was to analyse ACV biochemically and to study ultrastructural changes inflicted on the cercariae as a result of autoclaving, thus rendering it highly protective. Results of this study showed that approximately 100 microg protein and 44 microg carbohydrate were obtained from 10(3) cercariae. The predominant sugar was fucose. Galactose, glucose, manose, galactosamine and glucosamine were also detected. Threonine, glycine, serine and glutamic acid comprised approximately 53.7% of the amino acid residues of the protein. Ultrastructural study revealed preserved architecture of the cercariae. The tails were still attached to the posterior ends of the bodies. However, in others the tails were separated from the bodies and appear schistosomula like. There were also some morphological changes such as thinning of the pericortical envelop with appearance of surface pores.
Subject(s)
Amino Acids/analysis , Animals , Microscopy, Electron, Scanning , Schistosoma mansoni/drug effects , Schistosomiasis mansoni/immunology , Vaccines/chemistryABSTRACT
En este capítulo, se hace una sucinta descripción de los requerimientos moleculares y de los mecanismos involucrados en la respuesta a la administración de vacunas. Debido a que la bibliografía al respecto es extraordinariamente extensa, sólo se incluyen referencias de grandes revisiones de los temas, donde el lector interesado podrá encontrar mayor información. Esto citado por el autor a manera de introducción, los subtítulos en que se divide el trajo son: Infección e inmunidad; Fase inespecífica, no inducible; Fase inespecífica, inducida y sin memoria; Fase específica, inducida con memoria; Antígenos; Sistemas inmunocompetente (SIC); Inducción de la respuesta inmunológica; Anticuerpos; Respuesta humoral y protección; Respuesta celular y protección; Linfocinas; Linfocitos T Citotóxicos; Memoria inmunológica; Evasión de la respuesta inmunológica; Efectos adversos de la respuesta inmunológica; Competencia inmunológica y vacunación; y, Vacunación y control de agentes infecciosos
Subject(s)
Immunity/drug effects , Immunity/immunology , Mexico , Vaccines/administration & dosage , Vaccines/analysis , Vaccines/chemical synthesis , Vaccines/chemistry , Vaccines/classification , Vaccines/isolation & purification , Vaccines/pharmacology , Vaccines/physiologyABSTRACT
En el campo de la industria farmacéutica, las vacunas representan una fracción sumamente reducida en cuanto a volúmenes de operación y ventas, por lo que durante muchos años las compañias han mostrado muy escaso interés en promover su investigación y desarrollo por considerarlas como productos poco redituables. Contribuyó a esta situación el hecho de que la aplicación de estos productos tiende gradualmente a reducir el tamaño de las poblaciones que los requieren, una vez que se ha alcanzado el control o la erradicación de la enfermedad que se pretende prevenir. Además, por tratarse de enfermedades infecciosas, la mayor parte de los usuarios potenciales se encuentran en países en desarrollo, con escaso poder económico. Los biológicos en general y las vacunas en especial son productos que están en un proceso continuo de evolución y cambio. El fabricante de la vacuna se enfrenta a menudo con la necesidad de aplicar tecnología compleja y de alto costo para las etapas de desarrollo y de producción industrial del producto. Con algunas vacunas, el tamaño del mercado puede quizá cubrir escasamente el costo de la inversión para desarrollo. Esto ocurre sobre todo si el mercado potencial es pequeño o si la población a vacunar no tiene recursos para pagar los costos de adquisición. El procedimiento de control de calidad de vacunas es necesariamente complicado y laborioso y consume mucho tiempo y esfuerzo a causa de la duración de pruebas efectuadas en animales de laboratorio, que además son costosas y sujetas a su propio control interno de calidad. Aunque los criterio de laboratorio son satisfactorios para determinar la calidad de vacunas, este tipo de procedimientos se deben considerar en un contexto más amplio de evaluación de su inocuidad y eficacia en la población, en cuya consecución deben participar además otras autoridades sanitarias encargadas de llevar a la práctica los programas de vacunación
Subject(s)
Drug and Narcotic Control/methods , Drug and Narcotic Control/organization & administration , Research/classification , Research/trends , Mexico , Vaccines/analysis , Vaccines/chemical synthesis , Vaccines/chemistry , Vaccines/classification , Vaccines/pharmacology , Vaccines/supply & distributionABSTRACT
Las llamadas vacunas de nueva generación incluyen a aquellas que no se preparan con un enfoque tradicionalista, es decir no usan al patógeno completo: virus, bacteria, protozoario, etc. atenuado o muerto. Su desarrollo conjunta información inmunológica y los avances en las técnicas de biología molecular. Con este enfoque, las nuevas vacunas sólo incluyen algunas moléculas (nativas o recombinantes), parte de éstas (péptidos sintéticos) o en su defecto, anticuerpos anti-idiotipo que mimetizan alguna estructura original en el patógeno. Entre los factores que han aumentado el interés para este enfoque, destaca la accesibilidad a las técnicas de biología molecular, que han permitido sobrepasar las limitaciones del enfoque tradicional. Prácticamente todas las vacunas que actualmente se emplean fueron desarrolladas antes del advenimiento de la biología molecular y aunque sólo se han podido obtener un número limitado de ellas, han significado un gran logro científico, que erradicó ya una enfermedad (viruela) y está en vías de hacer lo mismo con otras (tétanos, difteria, tosferina, poliomielitis, sarampión, etc.). No obstante, aún faltan muchas vacunas para prevenir un gran número de enfermedades infecciosas cuya trascendencia en la salud puede ser muy seria como lo ejemplifica el avance epidémico del Síndrome de Inmunodeficiencia Adquirida. Se abordan los diferentes énfoques que varios investigadores han empleado para el desarrollo de las nuevas vacunas