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Wednesday, October 18, 2006

Up-to-date vaccines against Malaria.

Malaria LyfeCycle. CDC/USA, Courtesy.

After a scrupulous reading of the compact ones of 3 multinational last meetings: 2002 (Malaria Vaccines. 3 rd. MIM. Pan-African Conference on Malaria), 2004 (Malvac Meeting. Evaluation of Malaria Vaccines. Switzerland) and 2005 (2 nd Annual Forum:HIV/TB/Malaria. Durban-South Africa), associated to an understanding of the efforts of the transnational GlaxoSmithKline, some public institutions and Bill and Melinda Gates Foundation, around visions and efforts to elaborate an effective vaccine, against malaria, assault us several reflections: I) If as they have planned, they have ready for 2011, a long lasting vaccine, applicable to varied populations, affordable and safe in children younger than 1 year old (children are protected until the 5 months, for maternal antibodies), against Plasmodium Falciparum and P. vivax, this will become the scientific breakthrough of the last ten years and the participant institutions would pass to the history like builder of one of the best scientific/social/political/ achievement of this century: to save the lives of millions of children residents in endemic areas of malaria (Africa, India, southeast Asia, Center and South America, etc). One watch videos and conferences of related different activities, appreciating in the coordinators, detachment and love for the humanity. Task, of anonymous heroes, also. VMI (Vaccine Malaria Initiative), has 250 million dollars in funds. W. Ripley Ballou (one of the brains of recombinants vaccines of Glaxo), says : ...."today exist public and private funds without parallel".....and for 2011..."Malaria Delenda Est...." The malaria a disease to prevent and to cure, kills 1 million African children every year, true shame for a technological society whose elite strata are since many years, in capacity of impeding non alone the development of malaria, but of of many other transmissible illnesses, characteristic of the poor countries.

II) In the current efforts to make a vaccine against malaria, it is not already used, to generate antibodies using alive complete virus (Edward Jenner. 1798. First vaccine against the smallpox), dead or attenuated. Today, besides that known, it is preferred to opt for viral fractions (subunits) fractions or, synthetic peptides as antigénic determinants, transfer of genes, virus payees of genes, recognition of specific antigenic determinants (epitopes), by monoclonals or antiidiotypes antibodies, sophisticated adyuvants, DNA with multiple transferred genes. It has to be this way, because the generation of antibodies using old technologies, can be morbid under certain circumstances to the own guest (inmunosupressed, chronic inflammatories states, etc). Today, the antigenic determinants, epitopes, etc., are meticulously determined, based on their mobility or hydrophilic properties, locating them by means of antiidiotypes (specific molds of antigenic determinants), conditioning bigger inmunogenicity and smaller side effects. For if it was little -instead of one- they are rehearsed today vaccines with multiple antigenic determinants. In previous articles I have suggested the elaboration of a mutant vaccine, worked with mathematical models and calculated potential virtual epitopes. Some vaccines, use irradiated sporozoites and others : blocking of sexual gametes. The immune answer, built in millions of years, is being put to the nude, for a group of scientific and enterpreuners in a job that today is the forefront of the bio/inmune/microbiológic, knowledge. Talent, knowledge and constant innovation, for the goals and the invested funds.

III) Of those around 12 vaccines rehearsed against different phases of the biological cycle (exoerytrocitic/liver/intraeritrocytic), of Plasmodium falciparum and P. vivax, at the moment one of the most promising is RTS, S (recombinant, sporozoite) A (adyuvant) SO2 A, designed to generate antibodies against sporozoites recently entered to the organism after the bite of a mosquito, to objective of to destroy them and to impede their access to liver and later to red blood cells. For it, virus' segmented epitopes, from the surface of the sporozoites, are used as booster of the immune answer. The 2005, the medical magazine Lancet, published the results of clinical tests vaccinations of Phase I, led by the spanish physician Pedro Alonso (47 years old. University of Barcelona), to 2000 children (1-4 years old), from Mozambique : 3 doses. 1 dose, every month -with protective effects up to 1 1/2 years later, avoiding serious cases (including deaths), until in 49% of cases. Today, with the recombinant vaccine (GlaxoSmithKline. Leader: Joe Cohen), it is carried out another clinical test in 500 children smaller than 2 years, coming from Ghana. In the next years it is hoped to vaccinate to great scale to children younger than 1 year and by the 2010, clinical tests to great spread scale to achieve protective effects of long lasting duration. They are already carried out, pilots clinical studies in children smaller than 1 year. The world waits that after the 2011, will exist a before and a after. After this feat-model it will be possible to generate easily recombinant vaccines against Bartonella, Lehismania, South American Tripanosomiasis and other endemic illnesses.
Sofisticadas vacunas, contra la Malaria

Tras una escrupulosa lectura de los compactos de 3 últimas reuniones multinacionales : 2002 (Malaria Vaccines. 3 rd. MIM. Pan-African Conference on Malaria), 2004 (Malvac Meeting. Evaluation of Malaria Vaccines.Suiza) y 2005 (2 nd Annual Forum:HIV/TB/Malaria. Durban-South Africa), asociada a una comprensión de los esfuerzos de la transnacional GlaxoSmithKline, algunas instituciones publicas y la Bill y Melinda Gates Foundation, en torno a visiones y esfuerzos para elaborar vacunas efectivas, contra la malaria, nos asaltan varias reflexiones: I) Si como lo han planificado, tienen lista para el 2011, una vacuna de larga duración, aplicable a variadas poblaciones, accesible, eficáz en niños menores de 1 año (niños estan protegidos hasta los 5 meses, por anticuerpos maternos), contra Plasmodium Falciparum y P. vivax, este seria el evento cientifico de la ultima década y las instituciones participantes pasarian a la historia como articuladores de uno de los logros cientifico/social/politico/mancomunado, más importante de este siglo: salvar las vidas de millones de niños residentes en areas endémicas de malaria (Africa, India, Asia suroriental, Centro y Sudamérica, etc). Uno contempla videos y conferencias de distintas actividades relacionadas, apreciando en los coordinadores, desprendimiento y amor por la humanidad. Faena, de heroes anónimos, también. El VMI (Iniciativa de vacuna contra la Malaria), cuenta con 250 millones de dólares en fondos. W. Ripley Ballou (uno de los cerebros de las vacunas recombinantes de la Glaxo),dice “existen hoy fondos publicos y privados sin paralelo….y para el 2011:Malaria Delenda Est”. La malaria, enfermedad prevenible y curable, mata 1 millón de niños africanos cada año, verdadera vergüenza para una sociedad tecnológica cuyos estratos mas adelantados estan desde hace muchos años, en capacidad de impedir el desarrollo no solo de la malaria-sino de de muchas otras enfermedades trasmisibles, propias de los paises pobres.

II) En los esfuerzos actuales de forja de vacunas contra la malaria, no se estila ya, generar anticuerpos empleando virus vivos completos (Edward Jenner. 1798. Primera vacuna contra la viruela), muertos o atenuados. Hoy, además de lo conocido prefiere optarse por fracciones virales (subunidades), peptidos sintéticos de determinantes antigénicos, transferencia de genes, virus portadores de genes, reconocimiento de determinantes antigenicos especificos (epitopes), por anticuerpos monoclonales o antiidiotipos, adyuvantes sofisticados, DNA, con multiples genes transferidos. Tiene que ser asi, porque la generación de anticuerpos empleando tecnologías antiguas, afecta morbidamente en ciertas circunstancias al propio huésped (inmunosuprimidos, inflamaciones crónicas, etc). Hoy, se identifican meticulosamente los determinantes antigenicos, epitopes,etc., en base a su movilidad o hidrofilia, ubicándolos mediante antiidiotipos (moldes especificos de determinantes antigénicos), condicionando mayor inmunogenicidad y menores efectos colaterales. Por si fuera poco -en lugar de uno- se ensayan hoy vacunas con múltiples determinantes antigénicos. En articulos anteriores he sugerido la elaboración de una vacuna mutante, trabajada con modelos matemáticos de epitopes virtuales. Algunas vacunas, emplean hoy, esporozoitos irradiados y otras: bloqueadores de los gametos sexuales. La respuesta inmune, gestada en millones de años, esta siendo puesta al desnudo, por un grupo de cientificos/empresarios, en una gesta que hoy por constituye la vanguardia de conocimientos bio/inmuno/microbiológicos. Talento, sapiencia e innovación constante, por las metas y los fondos invertidos.

III) De las alrededor de 12 vacunas ensayadas contra distintas fases del ciclo biológico (exoeritrocitica/hepatica/intraeritrocitca), del Plasmodium falciparum y P. vivax, de momento una de las más prometedora es la RTS, S (recombinant, sporozoite) A (adyuvante) SO2 A, diseñada para generar anticuerpos contra los sporozoitos recien ingresados al organismo tras la picadura del mosquito, a objetivo de destruirlos e impedir su acceso a las células hepáticas y glóbulos rojos. Para ello, virus portadores de segmentos de epitopes, de la superficie de los sporozoitos, son utilizados como inciadores de la respuesta inmune. El 2005, Lancet, publicó los resultados de ensayos clinicos de vacunaciones de Fase I, lideradas por el medico español Pedro Alonso (47), de la Universidad de Barcelona, a 2000 niños (1-4 años), de Mozambique : 3 dosis -1, cada mes- con efectos protectores hasta 1 1/2 años después, evitando casos graves y muerte, hasta en un 49% de casos. Hoy, con la misma vacuna recombinante (GlaxoSmithKline. Joe Cohen), se realiza otro ensayo clinico en 500 niños menores de 2 años, procedentes de Ghana. En los próximos años se espera vacunar a gran escala a menores de 1 año y el 2010, ensayos clinicos a gran escala tendientes a lograr efectos protectores de mayor duración. Se realizan ya, ensayos pilotos en niños menores de 1 año. El mundo espera, que después del 2011, exista un antes y un después. Luego de esta hazaña/modelo se podrán generar fácilmente vacunas recombinantes contra Bartonella, Lehismania, Tripanosomiasis sudamericana y otras enfermedades endémicas
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