Viruses use these glycans mainly to hide from the human immune system; such measures are unnecessary in pigs and birds, which have shorter lifespans and tend not to be infected more than once. But in humans, adding sugars allows the virus to mutate and attack the same person multiple times. “Because humans live longer than one or two flu seasons, there’s more pressure on the virus to evolve mechanisms to escape antibody response, and one way to do that is by acquiring glycans,” says Richard Webby, who specializes in flu virology and ecology at St. Jude’s Research Hospital in Memphis, TN.
In the two pandemic viruses, the lack of glycans indicates a very recent jump from animals–so recent that they hadn’t yet had time to evolve. That worries Nabel. He is concerned that as the 2009 virus morphs, attaching sugars to better evade detection, it will become a more dangerous flu. When he and his collaborators forced the virus to evolve in the laboratory, attaching glycans to the sites where none currently exist, they found that the resulting viruses were resistant to the current H1N1 vaccine.
“That’s a great concern, because it says that it’s very likely this 2009 virus isn’t going to stop dead in its tracks. It’s going to find ways to outwit the human immune system,” Nabel says. In fact, he points out, it already has. Four strains of H1N1 have now been found in Russia and China that indicate the addition of glycans has already occurred, just as the researchers predicted.
But predicting evolution also means that it’s possible to vaccinate against it. When the researchers immunized mice against their lab-evolved strain of H1N1, the mice generated an effective immune response. “So we actually have a way of trying to anticipate what the virus might do, and developing vaccines that would be effective against the change,” Nabel says.
“We change the vaccine every year because these viruses drift so frequently. And yet, an important element of this particular virus was conserved for 90 years,” says the Mayo Clinic’s Greg Poland. “Now you have a marker to try and understand viral evolution and how that plays out in terms of the human experience with that virus.”
Nabel and others believe it could also inform vaccination protocol. If the cause of H1N1’s virulence was due to a lapse in our “herd” immunity, with too much time elapsed since the last time it circulated, the researchers propose that it might be worth considering regular vaccinations with prior pandemic strains–using history to predict viral evolution and inform vaccine development.