Adjuvants and delivery systems in veterinary vaccinology: current state and future developments

Modern adjuvants should induce strong and balanced immune responses, and it is often desirable to induce specific types of immunity. As an example, efficient Th1-immunity-inducing adjuvants are highly in demand. Such adjuvants promote good cell-mediated immunity against subunit vaccines that have low immunogenicity themselves. The development of such adjuvants may take advantage of the increased knowledge of the molecular mechanisms and factors controlling these responses. However, knowledge of such molecular details of immune mechanisms is relatively scarce for species other than humans and laboratory rodents, and in addition, there are special considerations pertaining to the use of adjuvants in veterinary animals, such as production and companion animals. With a focus on veterinary animals, this review highlights a number of approaches being pursued, including cytokines, CpG oligonucleotides, microparticles and liposomes. (Résumé d'auteur

Gene and cell therapy for cystic fibrosis: From bench to bedside

Clinical trials in cystic fibrosis (CF) patients established proof-of-principle for transfer of the wild-type cystic fibrosis transmembrane conductance regulator (CFTR) gene to airway epithelial cells. However, the limited efficacy of gene transfer vectors as well as extra- and intracellular barriers have prevented the development of a gene therapy-based treatment for CF. Here, we review the use of new viral and nonviral gene therapy vectors, as well as human artificial chromosomes, to overcome barriers to successful CFTR expression. Pre-clinical studies will surely benefit from novel animal models, such as CF pigs and ferrets. Prenatal gene therapy is a potential alternative to gene transfer to fully developed lungs. However, unresolved issues, including the possibility of adverse effects on pre- and postnatal development, the risk of initiating oncogenic or degenerative processes and germ line transmission require further investigation. Finally, we discuss the therapeutic potential of stem cells for CF lung disease. (C) 2011 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved

ANTITUMOR IMMUNOTHERAPY BY MELANA/MART1 ANTIGEN MESSENGER RNA TRANSFER.

An antitumoral response due to the induction of cytotoxic T lymphocytes can be generated after in vitro or directly in vivo transfer of tumor antigens mRNA in dendritic cells (DCs). However, few vectors allow an effective mRNA delivery into the DCs. We developed mRNA nanoparticles with histidylated cationic polymers (polyplexes), histidylated cationic lipids (lipoplexes) or a mixture of both (lipopolyplexes). These vectors become fusiogenic in acidic medium and favor the delivery of mRNA in the cytosol during endocytosis. An mRNA optimization by adding a cap 3'-O-méthyl-m75'GpppS'G (ARCA) in 5' and a tail of 100 adenosines (A100) in 3' led to the synthesis of an ARCA-ARNm-A100 transcript which allows a high antigen expression in DCs.,The histidylated polyethyleneimine was identified as a good transfection reagent for in vitro MART-1 melanoma antigen mRNA transfer in mature DCs. For a vaccination by direct injection of mRNA antigen, we developed news ternary nanoparticles (lipopolyplexes) corresponding to polyplexes of ARCA-MART1-A100 mRNA and a PEGylated derivative of histidylated polylysine encapsulated in histidylated liposomes. Systemic injections of these lipopolyplexes induce a specific and significant protective effect against cutaneous tumour and lung metastasis progression of B16FIO murine melanoma. The induction of Thl immune response with a strong secretion of IFN-y and a T cytotoxic activity, have been prouved showing the interest of histidylated lipopolyplexesUne réponse antitumorale suite à l'induction de lymphocytes T cytotoxiques peut être générée après transfert in vitro ou directement in vivo d'ARNm d'antigènes tumoraux dans les cellules dendritiques (DCs). Cependant, peu de vecteurs permettent une introduction efficace d'ARNm dans les DCs. Nous avons élaboré des nanoparticules d'ARNm avec des polymères cationiques histidylés (polyplexes), des lipides cationiques histidylés (lipoplexes) ou un mélange des deux (lipopolyplexes). Ces vecteurs deviennent fusiogènes en milieu acide et favorisent la délivrance de l'ARNm dans le cytosol lors de son endocytose. Une optimisation de l'ARNm en ajoutant en 5' une coiffe 3'-O-méthyl-m75'GpppS'G (ARCA) et en 3' une queue de 100 adénosines (A 100) a permis la synthèse d'un transcrit ARCA-ARNm-A 100 qui permet une bonne expression de l'antigène dans les DCs. La polyéthylèneimine hisidylée a été identifiée comme étant un bon agent de transfert de l'ARNm de l'antigène du mélanome MART-1 dans les DCs matures in vitro. Pour une vaccination par injection directe de l'ARNm codant l'antigène, nous avons développé de nouvelles nanoparticules tripartites (lipopolyplexes) correspondant à des polyplexes d'ARNm ARCA-MART1-A100 avec un dérivé PEGylé de la polylysine histidylée encapsulés dans des liposomes histidylés. Par injection systémique, ces lipopolyplexes induisent un effet protecteur spécifique et significatif contre la progression tumorale cutanée et métastatique pulmonaire du mélanome murin B16F10. La mise en place d'une réponse immune de type Thl avec une forte sécrétion d'IFN-y et une activité T cytotoxique a pu être mise en évidence montrant ainsi l'intérêt des lipopolyplexes histidylés

La programación del mantenimiento del alumbrado viario y el impacto en su eficiencia energética

Se presenta un estudio acerca de la influencia de las acciones de mantenimiento en las instalaciones de alumbrado viario. Se abordan los aspectos relacionados con las causas de depreciación de estos sistemas y las acciones de mantenimiento para su corrección. Se conceptualiza la eficiencia energética para el caso del alumbrado viario y se mencionan todos los aspectos relacionados con ello. Los autores llaman la atención acerca de que frecuentemente los análisis para incrementar la eficiencia de estos sistemas de alumbrado solo se centran en las posibilidades de cambio y mejoramiento de las lámparas, balastos, luminarias, así como las técnicas de regulación y control. En el artículo se hace énfasis en cómo a través del establecimiento del programa de mantenimiento que se defina se puede impactar en la eficiencia energética desde la etapa de diseño y durante su explotación, resaltando las potencialidades en esta vía poco estudiada hasta este momento.A study about maintenance actions influences in road lighting efficiency is presented. The aspects related with the causes of the luminous depreciation of road lighting systems and the maintenance actions are approached for their correction. The energy efficiency is conceptualized for the road lighting case and all the aspects can be impacted to increase it are mentioned. The authors emphasis stands out that attention that usually the analyses to increase the efficiency of these systems is frequently focused only on the possibilities of change and improvement of the lamps, ballasts, luminaries and the control and regulation techniques to increase the efficiency of road lighting. The paper analyses how through a maintenance schedule it can impact on the energy efficiency from the design stage and during their exploitation, standing out the potentialities in this way little studied until this moment

La programación del mantenimiento del alumbrado viario y el impacto en su eficiencia energética; The road lighting maintenance schedule and the impact in their energy efficiency

<p>Se presenta un estudio acerca de la influencia de las acciones de mantenimiento en las instalaciones de alumbrado<br />viario. Se abordan los aspectos relacionados con las causas de depreciaci&oacute;n de estos sistemas y las acciones de<br />mantenimiento para su correcci&oacute;n. Se conceptualiza la eficiencia energ&eacute;tica para el caso del alumbrado viario y se<br />mencionan todos los aspectos relacionados con ello. Los autores llaman la atenci&oacute;n acerca de que frecuentemente<br />los an&aacute;lisis para incrementar la eficiencia de estos sistemas de alumbrado solo se centran en las posibilidades de<br />cambio y mejoramiento de las l&aacute;mparas, balastos, luminarias, as&iacute; como las t&eacute;cnicas de regulaci&oacute;n y control. En el<br />art&iacute;culo se hace &eacute;nfasis en c&oacute;mo a trav&eacute;s del establecimiento del programa de mantenimiento que se defina se<br />puede impactar en la eficiencia energ&eacute;tica desde la etapa de dise&ntilde;o y durante su explotaci&oacute;n, resaltando las<br />potencialidades en esta v&iacute;a poco estudiada hasta este momento.</p><p>&nbsp;</p><p>&nbsp;</p><p>&nbsp;</p><p>A study about maintenance actions influences in road lighting efficiency is presented. The aspects related with the<br />causes of the luminous depreciation of road lighting systems and the maintenance actions are approached for their<br />correction. The energy efficiency is conceptualized for the road lighting case and all the aspects can be impacted to<br />increase it are mentioned. The authors emphasis stands out that attention that usually the analyses to increase the<br />efficiency of these systems is frequently focused only on the possibilities of change and improvement of the lamps,<br />ballasts, luminaries and the control and regulation techniques to increase the efficiency of road lighting. The paper<br />analyses how through a maintenance schedule it can impact on the energy efficiency from the design stage and<br />during their exploitation, standing out the potentialities in this way little studied until this moment.</p

Tendencias en la consideración de la depreciación luminosa de las lámparas empleadas en alumbrado viario; Trends in the consideration of lighting depreciation of lamps used in road lighting

La producción luminosa de las lámparas en alumbrado viario disminuye a un ritmo que depende del tipo de lámpara y balasto así como los parámetros de explotación. Esta causa de depreciación se considera desde la etapa de diseño a partir del factor de mantenimiento. El presente trabajo realiza una revisión de las diferentes fuentes de información disponible, a la vez que valora los resultados de las principales investigaciones que las han utilizado en los últimos tiempos. La información suministrada por los fabricantes de lámparas son la fuente más confiable. Los avances tecnológicos de las lámparas convencionales han permitido extender su vida útil e incrementar el mantenimiento del flujo luminoso lo cual potencialmente permite elevar la eficiencia energética de estos sistemas. Además de otras importantes ventajas los LEDs tienen un buen mantenimiento de su flujo luminoso. Se ofrecen los modelos matemáticos para la estimación de este tipo de depreciación. The luminous output of the lamps in road lighting decreases at a rate that depends on the type of lamp, the ballast system and operating parameters. This cause of depreciation is considered from the design stage from the maintenance factor, once established maintenance program. This paper reviews the different sources of information available, while valuing the outcomes of the major investigations that have been used in recent times. It recognizes the data provided by lamp manufacturers as the most reliable source. Technological advances introduced into the manufacturing process of these lamps in addition to extending its useful life also deliver higher lumen maintenance which potentially can increase the energy efficiency of these systems. In addition to other important advantages, LEDs has a good maintenance of their luminous flux The authors approach the trial elements and techniques for the use of curve fitting tool. Mathematical models to predict this depreciation rate are offered.</p

Estimado de la reducción de la emisión de co2 por accione de ahorro de electricidad en las condiciones de Cuba,

Este trabajo expone los resultados del estudio realizado a las numerosas v&iacute;as que existen para el c&aacute;lculo del factor de emisi&oacute;n de CO2 a nivel mundial. A partir de una amplia b&uacute;squeda de informaci&oacute;n, se obtuvo la metodolog&iacute;a propuesta para el c&aacute;lculo del factor de emisi&oacute;n de CO2 para proyectos de ahorro de energ&iacute;a el&eacute;ctrica, teniendo en cuenta las particularidades de la matriz energ&eacute;tica del pa&iacute;s en cuesti&oacute;n. La metodolog&iacute;a propuesta es el resultado de las modificaciones realizadas a la metodolog&iacute;a ACM 0002, que es la aprobada por la Junta Ejecutiva del Mecanismo de Desarrollo Limpio (MDL). A partir de los datos reales del consumo de combustible para la electricidad en Cuba en los a&ntilde;os 2007 y 2008, se calcula el factor de emisi&oacute;n de CO2, obteni&eacute;ndose un valor igual a 0,795 y 0,794 t CO2/MWh, respectivamente. Estos resultados evidencian el paulatino desarrollo hacia fuentes de energ&iacute;a mas limpias que se ha realizado en ese periodo en el pa&iacute;s, caracterizado por la entrada en funcionamiento de varios emplazamientos de Fuel-oil.&nbsp;This work exposes result of accomplished study to the many manners that exist for the calculation of CO2 emission factor in the world. Latter a ample quest of information, the proposed methodology was obtained for calculation of CO2 emission factor for electric power saving project, taking the particularities of electrical systems into account country. The proposed methodology is results of modifications realized to the methodology ACM 0002, this are the approved in Executive Board of the Clean Development Mechanism (CDM). Whit the real data of fuel consumption for the electricity in Cuba in the years 2007 and 2008, CO2 emission factor is calculated, obtained an equal value to 0.795 and 0.794 tCO2/MWh, respectively. These aftermath evidence the gradual development to cleaning sources of energy that success in period at the country, characterized for the entrance in functioning of several Fuel's-oil emplacements.</p

mRNA transfection of dendritic cells: synergistic effect of ARCA mRNA capping with Poly(A) chains in cis and in trans for a high protein expression level

The occurrence of translation mechanism in the cytosol offers advantages to mRNA transfer over DNA-based transfection in non-dividing cells. Here, we sought to optimize mRNA constructs allowing a high level of protein upon lipofection. We found that luciferase into mouse dendritic cells (JAWSII cells) was not, vert, similar20-fold higher when the luciferase mRNA was capped with 3′-O-methyl-m75′Gppp5′G (anti-reverse cap analogue; ARCA) than with m75′Gppp5′G (CAP). Adding a Poly(A) tail of 100 instead of 64 adenosines in cis increased by not, vert, similar35-fold more the protein level. Finally, ARCA-Luc-mRNA-A100 construct was 700-fold better efficient than the CAP-Luc-mRNA-A64 one. Moreover, co-transfection with free Poly(A) chains in trans enhanced by 100% the luciferase level. The efficiency of ARCA-mRNA-A100 construct was validated in immature and mature human CD34-derived dendritic cells. Such mRNA construct was also successful to obtain high level of MART-1 tumor antigen