Can Vaccination Help Fight Influenza of the Future?

Research suggests it limits flu evolution, bringing greater public benefits

Each year, influenza infects 20 to 30 percent of the world’s children and 5 to 10 percent of its adults, causing as many as a half million deaths. Even here in the United States, where severe responses to the flu are generally restricted to the very young and very old, the flu costs our economy as much as $87 billion a year. Thus many Americans choose to be inoculated every year against the flu, in the hopes of avoiding the discomfort and wasted work days an onset of the illness can bring. But is this the right decision?

According to Anup Malani, Lee and Brena Freeman Professor of Law at the University of Chicago Law School, the answer is an overwhelming yes. At a recent Becker Brown Bag, Professor Malani noted in his talk, “Vaccination Policy and Antigen Drift in Influenza A,” that there are two benefits from getting a flu vaccine: The private benefit is that it decreases the chance of the inoculated patient getting sick. The second is that if individuals avoid the flu, that reduces the likelihood of infecting others around them, so the public benefits.

What’s more, his new research suggests that higher vaccination rates may limit the evolution of the flu, so the virus is less likely to mutate beyond the bounds of immunity.

Unlike illnesses like chicken pox and German measles, the seasonal or common flu, a viral strain known as H3N2, mutates over time, which explains why there is a new vaccination against it each flu season. Most research on the evolution of the flu—and current economic estimates of the value of vaccination—studies how natural immunity affects drift and variation and how vaccination affects infection rates.

But for the decades, most research on evolution of the flu —and current economic estimates of the value of vaccination—has studied the mutations only in relationship to how they relate to the naturally acquired immunity patients get to the flu after they have been sick, Malani said. The literature assumes that getting a flu shot does not affect drift and variation in the illness. That does not make theoretical sense, Malani told the group. Because a flu shot stimulates immunity, it should affect flu evolution in the same way getting the flu does.

So Malani and his research partners, assistant professor Sarah Cobey and doctoral student Frank Wen in the UChicago Department of Ecology and Evolution, modified a standard model of how the flu evolves to include the effects of vaccination, running simulations of vaccinated individuals.

Uniquely, Malani pointed out, “H3N2 only moves in two dimensions and tends to go in a straight line in genetic space.” This means that it is possible to predict how the flu will mutate in coming years. It also means that when an individual is vaccinated against a particular year’s flu, that immunity may help that person stay healthy for another year or two because because next year’s virus is not radically different.

Their simulation showed that greater vaccination rates within a population reduces the average drift of mutation—a finding that lines up well with observed data. If vaccination limits the evolution of flu, the social benefit is even larger, because fewer people will face a strain that makes them ill, and fewer non-vaccinated people will be exposed.

“In addition to preventing more people from getting sick, vaccination also seems to slow the evolution of the flu,” Malani explained. “In fact, once you hit 10 percent vaccination globally, the flu goes extinct. But that is really hard to do.” Most flu strains originate in Asia, where vaccination rates are very low. “Iit is a really large world and we just don’t have the infrastructure to do it,” he noted

Unfortunately, this strong social benefit of vaccination also has a downside—a free rider problem. As the public benefit of vaccination increases, the private benefit declines. As vaccination reduces the evolutionary drift and fewer people get sick, more individuals may feel there is little risk and skip the flu shot.

Thus there is another possible caveat to the findings, Malani said. If the breadth of immunity from the vaccination is smaller than from natural infection, there is the possibility the viral strains surviving after vaccination are those that mutate more, making bigger jumps outside the zone of immunity. That raises the possibility that the North American version of the flu could end up seeding the rest of the world, rather than the other way around as it does today.

“The rest of the world has no vaccination, and that is where most of the evolution is happening,” Malani said. If vaccination in the US and Western Europe causes greater evolution, “the flu in the rest of the world is going to change more quickly. We only need a little travel to have a faster mutating version moving around the globe,” Malani explained.

Malani pointed out several next steps he and his colleagues are pursuing to expand and strengthen their research. Yet the findings thus far point out the importance of including the evolutionary effects when calculating the economic benefits of vaccination and considering vaccination policies.

—    Robin Mordfin