ANTIGENIC CARTOGRAPHY: The distance between viruses (colored shapes) represents how similar they are to each other. The shape indicates the precision with which the virus can be located. Image: Courtesy of the University of Cambridge (U.K.) Department of Zoology
In the same way that a road map helps drivers make sense of otherwise cryptic directions, a team of scientists has developed software that allows them to map the clashes between immune systems and germs, starting with the influenza virus. This integration and illustration of data culled from laboratories around the globe marks a major step toward understanding and combating a virus that typically claims more than 250,000 lives worldwide annually, according to the World Health Organization (WHO).
The raw data for these antigenic maps comes from the WHO Global Influenza Surveillance Network of more than 100 laboratories in 80 countries that test about 5,000 influenza strains annually. Researchers enter this data into a Web site secured by data encryption and passwords, where it becomes available to four international WHO collaborating centers—in the U.S., Australia, Japan and the U.K.—that analyze the strains against different antibodies, which are protein molecules formed by the immune system to identify and neutralize bacteria, viruses and other intruders.
Flu vaccines work by introducing the body to inactive strains of a recent flu virus. But before scientists can decide which strains of flu to use in a vaccine, they must first determine how the body's immune system reacts to the different flu strains it encounters. This difference between viruses—as our immune system interprets them—is known as the "antigenic difference," says Derek Smith, professor of infectious disease informatics at the University of Cambridge's Department of Zoology, who wrote the antigenic cartography software in collaboration with Alan Lapedes, a computational biologist at Los Alamos National Laboratory in New Mexico, and Ron Fouchier, a virologist at the Erasmus Medical Center in Rotterdam, the Netherlands. "You take antibodies raised for different strains of flu and see how well they bind to different strains of influenza," he adds, "and you end up with a table with these measurements."
Numbers representing these antigenic differences have for decades been presented in tables so that researchers can compare the results. But Smith says that it takes "expertise to be able to read these tables."
In addition to Lapedes and Fouchier, Smith credits the emergence of antigenic cartography to the work of Jan de Jong, a researcher in Erasmus's Department of Virology, who collected data on flu strains dating back to 1968; Albert Osterhaus, an Erasmus professor of virology who funded and encouraged the early work on the mapping project; and Nancy Cox, director of the U.S. Centers for Disease Control's Influenza Division.
Smith and his colleagues first described their antigenic cartography technique in a 2004 Science article. They have since used their software to create an antigenic map that documents 13,000 human flu strains isolated over the past five years. When these results are plotted on a digital antigenic map, researchers can see in fine detail how the body's immune system responds to different mutations of the virus. "Cartography increases the resolution at which these [differences] can be judged," says Smith, who earned a PhD in computer science from the University of New Mexico in Albuquerque while a fellow at the Santa Fe Institute.
The influenza maps are just the beginning of what health care professionals hope will become a series of useful visual aids. "By applying an innovative strategy to map differences in seasonal influenza strains worldwide, Smith and his colleagues have offered important insights into patterns of influenza virus spread that could greatly improve surveillance and vaccine strain selection," Elias Zerhouni, director of the U.S. National Institutes of Health, which funds the mapping project through its Pioneer Award program, said in a statement.
Researchers are already at work on antigenic maps of malaria and rabies, and there are plans for HIV and dengue maps as well. "We built antigenic cartography because flu was our primary love," Smith says, "but it needed to apply to other pathogens." To meet these needs, the researchers plan to release an "open-source" version of their software over the next six to nine months on the Web that computer programmers and researchers will be able to use and modify for their own projects. The price tag? Zip—according to Smith, who notes the hope is that they share their findings and modifications with the software's other users.
Instead of sending their data-laden digital spreadsheets to Cambridge, where the researchers' cluster of 20 computer servers run the antigenic cartography software that makes the maps, researchers will be able to run the mapmaking software on their own computers. "Our goal," Smith says, "is to make antigenic cartography [that sits] on people's desktops so they use it without even knowing who wrote it."