Washington: Development of an effective HIV vaccine has so far failed, mainly because the virus evolves so rapidly that it can evade any vaccine-induced immune response.Now, a researcher team led by an Indian origin scientist has developed a new approach to vaccine design that may allow them to cut off those evolutionary escape routes.The researchers from the Ragon Institute of MGH, MIT and Harvard University have developed and experimentally validated a computational method that can analyze viral protein sequences to determine how well different viral strains can reproduce in the body. That knowledge gives researchers an unprecedented guide for identifying viral vulnerabilities that could be exploited to design successful vaccine targets.The team, led by Arup Chakraborty, the Robert T. Haslam Professor of Chemical Engineering, Chemistry, Physics and Biological Engineering at MIT, has designed protein fragments (peptides) that would target these weaknesses.Ragon Institute researchers are now developing ways to deliver the peptides so they can be tested in animals."We think that, if it continues to be validated against laboratory and clinical data, this method could be quite useful for rational design of the active component of a vaccine for diverse viruses. Furthermore, if delivered properly, the peptides we have designed may be able to mount potent responses against HIV across a population," said Chakraborty, who is also the director of MIT`s Institute for Medical Engineering and Science.Typically when a vaccine for a disease such as smallpox or polio is given, exposure to viral fragments primes the body`s immune system to respond powerfully if it encounters the real virus. With HIV, it appears that when immune cells in a vaccinated person attack viral peptides that they recognize, the virus quickly mutates its protein sequences so immune cells no longer recognize them.To overcome this, scientists have tried analyzing viral proteins to find amino acids that don`t often mutate, which would suggest that they are critical to the virus`s survival. However, this approach ignores the fact that mutations elsewhere in the protein can compensate when those seemingly critical amino acids are forced to evolve, Chakraborty said.The Ragon Institute team focused on defining how the virus`s ability to survive depends on the sequences of its proteins, if they have multiple mutations. This knowledge could enable identification of combinations of amino acid mutations that are harmful to the virus. Vaccines that target those amino acids would force the virus to make mutations that weaken it.With existing HIV protein sequence data as input, the researchers created a computer model that can predict the fitness of any possible sequence, enabling prediction of how specific mutations would affect the virus.
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