Antigenic map of influenza A (H3N2) virus from 1968 to 2003. Clusters are named after the first vaccine-strain in the cluster. The two letters refer to the location of isolation (Hong Kong, England, Victoria, Texas, Bangkok, Sichuan, Beijing, Wuhan, Sydney and Fujian) and two digits refer to the year of isolation. Strain color represents the antigenic cluster to which the strain belongs. The vertical and horizontal axes both represent antigenic distance, and because only the relative positions of antigens and antisera can be determined, the orientation of the map within these axes is free. Graphic created by R.A.M. Fouchier, copyright Science (permission granted for use). A Laboratory scientist working with collaborators from the University of Cambridge (England) and the World Health Organization National Influenza Center at Erasmus Medical Center, (Rotterdam, Netherlands) have developed a computer modeling method for mapping the evolution of the influenza virus. The method could soon help medical researchers worldwide develop a better understanding of certain mutations in influenza and other viruses that allow diseases to dodge the human immune system. In a paper published in today's edition of the journal Science, the team of scientists from the United States and Europe describe their work quantifying and visualizing the antigenic and genetic evolution of the influenza A (H3N2) virus from its initial introduction into humans in 1968 up to 2003. The study resulted in a map that shows the virus evolved as a series of 11 closely related virus clusters as it has sought to elude human immunity over the decades.
The mapping method will allow researchers involved in vaccine development and viral surveillance programs for influenza, and potentially for other pathogens such as Hepatitis C and HIV as well, to quantify and visualize the evolution of these viruses. It can assist in monitoring antigenic differences among vaccine and circulating viral strains, and can help in quantifying the effects of vaccination. The approach also offers a route for predicting the relative infection success of emerging virus strains.
According to Los Alamos computational biologist Alan Lapedes, "This collaboration was particularly exciting because it involved close interaction between experts in computation and virology and medicine. Once we had created the map, we tested its reliability by making hundreds of predictions of how well certain strains might match up and then conducting laboratory tests to check the predictions. It's very gratifying that this basic research also has practical application to an important human pathogen, influenza."
Experts estimate that influenza epidemics cause an estimated 500,000 human deaths worldwide each year. Although antibodies provide protective immunity to influenza virus infection, the antigenic structure of proteins that stimulate immune responses changes significantly over time, a process known as antigenic drift, so in most years the influenza vaccine has to be updated to ensure sufficient efficacy against newly emerging variants.
In addition to Lapedes, of Complex Systems (T-13), the team members included Derek Smith from the University of Cambridge, and Ron Fouchi, Jan de Jong, Theo Bestebroer, Guus Rimmelzwaan and Albert Osterhaus from National Influenza Center at Erasmus Medical Center.
Funding for the Los Alamos portion of the research was provided by Los Alamos' Laboratory-Directed Research and Development (LDRD) program. LDRD funds basic and applied research and development focusing on employee-initiated creative proposals selected at the discretion of the Laboratory director.