Antigenic cartography is a scientific method used to visualize the evolving properties of pathogens, such as influenza. This technique creates a map that illustrates the relationships between different virus strains from the immune system’s perspective. It translates complex biological data into an intuitive, spatial format, allowing researchers to see how much one strain “looks” like another to the antibodies that fight them.
These maps quantify and visualize subtle differences between viral strains, an approach useful for tracking viruses that change rapidly. By plotting these changes, scientists can observe a virus’s evolution and identify how it alters itself to evade pre-existing immunity in the population.
The Core Concept of Antigenic Mapping
The foundation of antigenic mapping is a virus’s antigenic properties, which determine how it is recognized by the immune system, rather than its genetic code. The map visualizes “antigenic distance,” a measure of how effectively antibodies generated against one virus can neutralize another. A small distance implies the two viruses are antigenically similar, meaning immunity to one would likely offer protection against the other. A large distance indicates the viruses are distinct to the immune system.
This concept revolves around the interaction between viral proteins, known as antigens, and the antibodies produced by the host. For the influenza virus, a primary antigen is the hemagglutinin (HA) protein on its surface, which antibodies are designed to bind. The map quantifies the strength of this binding across numerous combinations of virus strains and antibody-containing preparations, called antisera.
While genetic analysis can show how a virus’s DNA or RNA is changing, it may not predict how those changes affect its interaction with the immune system. A single amino acid change on an antigen could cause a significant shift in its antigenic properties, a detail captured by antigenic cartography but potentially missed by genetics alone.
Creating the Antigenic Map
Creating an antigenic map begins with the hemagglutination inhibition (HAI) assay. In this test, scientists take a collection of different virus strains and mix each one with a panel of antisera. This antisera is generated by exposing an animal, such as a ferret, to a single virus strain, causing it to produce a specific set of antibodies. The HAI assay measures how well these antibodies prevent the virus’s hemagglutinin protein from binding to red blood cells.
The results from these tests are compiled into a large table of numerical values, or a matrix. Each number represents a specific virus-antiserum interaction, indicating how effectively a set of antibodies inhibited a virus strain. This table provides the raw data, but the overall patterns of antigenic relationships are difficult to discern in this format.
This laboratory data is then processed using computational software. A mathematical technique called multidimensional scaling (MDS) translates the numerical relationships from the data table into a two or three-dimensional spatial map. The algorithm positions each virus strain and antiserum on the map so the distance between any two points corresponds to the antigenic distance measured in the lab.
Interpreting the Visuals
Reading an antigenic map involves understanding its components. Each point on the map signifies a specific virus strain, while other shapes, such as open circles, represent the antisera used in the laboratory assays. The map is overlaid with a grid, where the space between each line represents one unit of antigenic distance. This unit corresponds to a twofold change in the concentration of antiserum required for inhibition in the HAI assay.
This grid provides a scale for quantifying the differences between strains. For example, two strains separated by two grid units have an antigenic distance of two units. Over time, the positions of new viral isolates can be added to the map. A path of points moving across the map from one year to the next is a visual representation of antigenic drift, the gradual evolution of the virus.
Researchers also look for clusters of points, which indicate groups of antigenically similar viruses circulating at the same time. The naming of these clusters is based on the location and year of the first isolation of a representative strain.
Practical Applications in Public Health
Antigenic cartography is a tool in global public health for the annual selection of influenza vaccine strains. Twice a year, the World Health Organization (WHO) recommends the composition of the influenza vaccine for the upcoming seasons. These maps are a primary piece of evidence in this process, providing a clear visual of which virus strains are circulating and how they relate to the previous season’s vaccine strain.
By examining the map, experts can identify which viral clusters have drifted furthest antigenically from the current vaccine strain. These drifted viruses are the ones most likely to evade immunity from the previous year’s vaccine, making them candidates for inclusion in the new formulation. The maps allow scientists to see the virus’s past evolution and anticipate its future trajectory, helping select a vaccine strain that will offer the best possible protection.
The utility of antigenic cartography extends beyond influenza, as this method has been adapted to study other evolving pathogens like SARS-CoV-2. For these viruses, the maps help track the emergence of new variants and assess their potential to escape immunity from prior infection or vaccination. This information aids public health officials in monitoring outbreaks and making informed decisions about booster shots and other strategies.