PULLMAN – A team of WSU scientists has devised a method that could lead to the development of vaccines against some of the most troubling infectious 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.
, 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.
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’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.
Once the genes were isolated, Brown’s team made the proteins they coded for by using chemical ‘machinery’ derived from E. coli bacteria. They then purified each protein to get rid of any E. coli proteins that were present.
Each purified test protein was then presented to T cells from cows that had previously been exposed to Anaplasma outer membrane proteins. T cells are the immune system’s “memory cells.”
Using the new procedure, Brown’s team found T cells responded to about 20 proteins, including many that had never before been shown to stimulate a T cell response. The researchers are now testing whether any of these might form the basis for an effective vaccine against Anaplasma.
Brown said the new technique also will be a boon to researchers working on vaccines against pathogens that are highly contagious or especially deadly, such as the Ebola virus and the bacterium that causes anthrax.
She is using it to screen proteins from Coxiella, a bacterium that causes Q fever and is considered a possible bioterrorism threat.
“If you have the genome, you don’t have to touch the organism. You can just start expressing all these proteins and test them,” Brown said.
