The La Jolla Institute for Allergy and Immunology (LIAI), a nonprofit organization that recently relocated on the University of California, San Diego campus, announced a successful computer-simulated immune response to the vaccinia virus, the agent used to eradicate the smallpox virus. This project, called “bioinformatics,” verified 95 percent of the total immune response to the virus in lab mice using data input into a software program.
Alessandro Sette, Ph.D., senior investigator on the project, said that the results are meaningful for several reasons.
¦This shows, in principle, that similar methodologies can be applied in humans to identify [a] response to [an] experimental vaccine,” he said.
His statement implies that new vaccines could be developed based on the new bioinformatics technology. Previously, scientists thought an immune response was unpredictable, and, therefore, a computer simulation would be impossible.
The study also suggests that it is possible to quickly compare and predict the potency of a vaccine to a virus when several viable options are considered.
“So if you have multiple different vaccine candidates, then you can quickly and reliably measure an immune response and know exactly what the immune response is induced by the vaccine,” Sette said.
Magdalini Moutaftsi, a postdoctoral researcher in Sette’s laboratory, conducted most of the experiments for the project.
She said, “[This is] something never done before because [immunologists] originally only looked at individual genes.”
For this reason, immunologists had only been able to map the immune response of small viruses.
In this set of experiments, she analyzed the entire genome of a mouse for possible immune responses to the vaccinia virus, one of the largest viruses in existence. Of the approximately 2,000 peptides identified as possible immune-system triggers to the virus, only 49 cause the immune system to react. These 49 peptides are considered “epitopes,” or structures that are recognized by the immune system. Moutaftsi said that the immune system cannot recognize the whole virus protein, but it can recognize the individual eptitopes that she identified.
Before this computer-simulated process was verified with that of a mouse, the steps used to identify an immune response were time-consuming.
“This way, by using bioinformatics, we simplify everything,” Moutaftsi said. ” “¦ Before, we just looked at one gene or five or six genes or proteins”¦in this study, we study the whole pathogen.”
Moutaftsi and Sette also have a group of researchers in their lab who enter information into the bioinformatics database daily. Scientists both inside and outside of LIAI report information about relevant epitopes to the lab. This information comes from their own experiments or from peer-reviewed immunology literature. Once reported, information must be verified for accuracy and then entered into the database.
“They are reading the papers [the published literature],” Moutaftsi said. “They are extracting the sequences in the papers ” the epitopes “¦ they put in what kind of assays those epitopes were identified [in].”
Scientists from all over the world can submit data to the database if it passes tests for accuracy. The Sette lab uses this newly compiled data to study simulated immunological responses to other pathogens as well.
“The next step up would be to really be able to tackle bacteria, which are, I would say, probably 20 to 100 times more complex than even the most complex virus,” said Sette, who wants to continue to work on other viruses as well.
“There are many important viruses that have not been studied,” he said.
For example, the flu virus has not been studied thoroughly in birds. This is a public health concern with the rising risk of avian flu in the United States.
“In general, I think that there is a lot of interest in developing the technology to be able to look at the format of vaccines and diagnostics, not only in humans and in laboratory mice, but more broadly,” he said.
Sette described the computerized prediction of the smallpox immune response as a tool ” a set of technologies to be used. The database stores the results of many past experimental analyses done by many different scientists.
“So, short of going to the library and reading 3,000 different papers of flu disease “¦ now the researchers can access the database “¦ and put in whatever search parameters and extract information that he/she needs,” Sette said.
National Institutes of Health (NIH) and LIAI funded this basic research study. Like most basic research studies, it does not have an immediate reward associated with it ” it merely serves to further basic knowledge in society. Of this type of research, Sette said, “Those are the ones that oftentimes have the most dramatic impact on the knowledge and future research “¦ and things that can be applied later on down the line.”
Perhaps it is the foresight of investigators like Sette that will, one day, allow all vaccines to be mapped by a computer.