A team of Washington State University scientists has devised a method that could lead to the development of vaccines against some of the most troubling infectious diseases we face diseases that have so far been difficult or impossible to vaccinate against.
The new method allows researchers to rapidly screen large numbers of pathogen proteins, called antigens, for their ability to prompt an immune response in a host. Proteins with that ability are good candidates for use in vaccines. The method will be especially valuable in the quest for vaccines against persistent diseases such as malaria, sleeping sickness and syphilis.
“It's very slick,” said immunologist Wendy Brown, who led the research effort. “Now we have a high-throughput way of finding antigens from any pathogen, as long as you have the genome sequence. To me this was a huge breakthrough, because I've been spending my whole career trying to figure out ways to do this.”
The research team included scientists at WSU and at the Rocky Mountain Laboratories of the National Institutes of Health. Their paper was published in the March 20 issue of the Journal of Immunological Methods and is available online at http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6T2Y-4RPD1TP-2-F&_cdi=4931&_user=137179&_orig=browse&_coverDate=03%2F20%2F2008&_sk=996679998&view=c&wchp=dGLbVzW-zSkWb&md5=c5df3cf715d25fc2884d90f4959ba3b3&ie=/sdarticle.pdf>.
A vaccine works by showing the body's immune system a pathogen or part of a pathogen (usually a protein) so that it can develop cellular memory and antibodies that will recognize and attack the pathogen in the future. A key step in the development of a vaccine is identifying which protein(s) to use. Until now, screening pathogen proteins to find those few that might be good candidates has been laborious, time-consuming, and in the case of persistent diseases, not very successful. Brown said prior methods required about three months to produce and purify a single protein to test. With her new method she is able to screen dozens of proteins within a few weeks.
Brown's group worked with Anaplasma, a bacterium that causes severe anemia in cattle. Anaplasma is the most common tick-borne pathogen of cattle worldwide and costs an estimated $100 million per year in lost animals and lowered productivity in the United States alone.
The new method starts with the pathogen's DNA. Previous work by WSU scientists had determined the whole genome sequence of Anaplasma. By comparing that sequence with the genome sequences of better-known microbes, Brown's team was able to pinpoint genes that code for proteins that stick out of the pathogen's cell membrane. Brown reasoned that since those proteins are exposed on the surface of the cell, they should be visible to antibodies and immune system cells, and therefore could be a good way to target the pathogen.