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studied protein of dengue vaccine development


The Venezuelan Institute for Scientific Research (IVIC) running project with Cuba

To date, there is no effective treatment to protect people against mosquito bites "white legs."

By Vanessa Ortiz PiƱango

vortiz@ivic.ve

viruses, in addition to being mortal, can go unnoticed in the human body for a long time, this is the case of dengue that despite being an infection of old data, has no specific treatments or diagnostic methods that allow early attack symptoms from the beginning.

dengue virus is transmitted by the bite Aedes aegypti mosquito, known as "white leg", causing of Dengue Fever (DF), the of Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS), the global climate change The population growth and failure in basic services such as water supply and waste disposal have led to the resurgence of this infection vector whose incidence has increased over the last twenty years.

Because of this situation, in 2006 the Venezuelan Institute Scientific Research (IVIC) established cooperative projects with the Center for Genetic Engineering and Biotechnology (ICGEB) of Cuba to develop vaccines for the control and treatment of emerging diseases (newly discovered or increase in the population) and re-emerging (apparently controlled ), with emphasis on dengue, hepatitis and HIV / AIDS. The bi-national initiative is in its second year of implementation and those responsible for the Centre of Microbiology and Cell Biology IVIC are Dr. Ferdinando Liprandi, head of the Laboratory of Biology of Viruses, and Flor Pujol, head of Laboratory Molecular Virology. L I experiments involved combining advanced scientific technologies as molecular biology, bioinformatics and virology.

Goodbye "white leg"

Dengue is a serious public health problem because of its tendency to spread rapidly in tropical countries like ours, where environmental conditions make the four serotypes recognized to date are moving simultaneously. First, it represents a serious threat to the Caribbean nations Venezuela and Cuba, where there have been four major outbreaks of epidemics in the past three years: 1977 and 1981 to nationally, 1997 in Santiago de Cuba and 2003 in Havana. In second place, because to date there is no effective vaccine to induce protection against all four serotypes the virus, the mosquito control the costly and inefficient and there is no diagnostic method capable of detecting infection occurred within hours after the bite of "white legs."

One aspect to be considered when evaluating the development of a dengue vaccine is the existence of four serotypes (1, 2, 3, 4), which means that the protection induced to one serotype will not work in another. That is, if a patient with dengue type 1 vaccine, will likely for the three remaining serotypes. "The problem is not just that you are still susceptible, but if you become infected with one dengue virus of another type, you run greater risk of evolving into the most severe form of disease," said Dr. Ferdinando Liprandi, head of Virus Biology Laboratory at IVIC. Hence the most feasible scheme is the creation of four vaccines, one for each serotype.

The problem raised by the review team is to understand the role of a protein, located on the surface of of dengue virus-immune response in the patient or guest, and confirm whether this response induces some protection against infection. "One of the instruments available are synthetic virus called infectious clones, which can be manipulated genetically to be used for purposes of vaccine or to try to answer questions. We in Venezuela produce the virus to see if the immune response recognizes the changes induced, while the Cuban counterpart checks whether the modified protein in the laboratory is recognized by the immune response, "he said.

This information will identify which sections of the protein are important for generating an effective response against all four serotypes the virus. To do this, they are collecting sera from infected individuals to show whether the changes caused by viruses and protein impact the patient's defensive response and how they do it.

Another important contribution of the project is the search for more effective diagnostic methods than those used today, which detect the presence of the virus only at the end of the acute phase of infection and even when patients are convalescing. That is, a method Late "which confirms the cause of the disease. Normally there is no way of knowing until after five or six days after the onset of symptoms, "said Dr. Liprandi.

two years ago launched a new concept in diagnosis based on detection of a protein the virus (NS1) entering the bloodstream during the febrile stage of the disease. "The virus multiplies in various tissues of host and as a result of this multiplication blood enters a viral protein. The diagnostic system is based on detecting, in a blood sample, the presence of this protein, which can help control the disease and its more severe manifestations as hemorrhagic fever.

The method consists of a commercial kit that allows the detection of the protein via an enzyme-linked immunosorbent assay, known as ELISA for its acronym in English (Enzyme- Linked immunoabsorbent Assay). There are two versions, one French and one Australian, " but I think that in future there will be more versions of this test is to be universal, because it is the new paradigm in the diagnosis of dengue." Its validation test was proposed and sponsored by the World of Health Organization (WHO) "and now we are validating, the first point is to show that this principle works, that early diagnosis is possible, and evaluate its sensitivity and specificity. When finished, use can be recommended to the Ministry of Popular Power for Health . " This extension of project is run of Dr. Alvaro Ramirez, a researcher at the postdocs Virus Biology Laboratory at IVIC.

In the case of the virus of "white leg" vaccine production is more complicated, because no animal is possible to reproduce the infection in all its dimensions, "the model that comes close is the mono, which does not develop the disease, but viremia is ie, presence of virus in blood. It has been used as parameter, but is far from the clinical manifestation is seen in humans, both in its classical form as hemorrhagic. He acknowledged that there is a global effort which has involved hundreds of laboratories, but "our work will not lead to an immediate product as the vaccine is what we are trying to answer a key question to advance the design itself. " Back


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