Although they emerged more than 90 years apart, the influenza viruses responsible for the pandemics of 1918 and 2009 share a similar structural detail and the 2009 H1N1 virus more closely resembles the 1918 Spanish flu virus than more modern cousins in the same flu family.  This new study by the U.S. National Institute of Allergy and Infectious Diseases (NIAID) confirms that antibodies that protect against the pandemic virus also fight the virus that caused the 1918 pandemic. However, they are not able to neutralize seasonal H1N1 viruses, nor do antibodies generated in response to those recent viruses stop 2009 H1N1 viruses.

The fact that two viruses that emerged 91 years apart would be so similar that antibodies which fight one can fight the other came as a surprise to the authors of the paper.  “It’s very rare for viruses that are separated by more than a couple of years to cross-neutralize,” said Gary Nabel, M.D., Ph.D., a scientist with the U.S. National Institute of Allergy and Infectious Diseases (NIAID). The findings also helps to explain why older individuals seem to have a degree of immunity to the pandemic H1N1 and why years of exposure to seasonal H1N1 viruses didn’t protect younger people from the new virus when it started spreading last year.

Seasonal H1N1 viruses and the pandemic virus that emerged last spring descend from the same ancestor -- the 1918 Spanish flu virus. But where seasonal viruses have evolved in people over decades, the pandemic H1N1 emerged from pigs -- a host that doesn't push flu viruses to change as rapidly as they do in humans.

The human immune system learns to mount defenses against flu viruses, forcing the viruses to alter themselves in order to evade those defenses. In the interplay between flu viruses and pigs, it’s the pigs that keep changing because of their short lifespan. Since they change, the viruses don’t need to. In essence, it’s like the pandemic H1N1 virus was frozen in time or in this case pigs.

Nabel’s lab looked at the structure of the key protein on the outside of flu viruses – the H or the hemagglutinin. While looking at the head of that protein, researchers found striking similarities between the 1918 virus and the 2009 H1N1 virus. When they compared them to contemporary seasonal H1N1 viruses, they noticed the seasonal viruses all had developed a pair of sugar coats on the head of the hemagglutinin. It is something flu viruses are known to do to help them evade the immune system. Those small changes and others render the virus unrecognizable to antibodies generated by related flu viruses.

Disguise Glasses
The lead researcher gave such a great example, with a disguise theme…"It's kind of like a celebrity wearing a hat on the airplane," Nabel explained.

Antibodies against the 1918 and 2009 viruses couldn’t recognize H1N1s that had those sugar coats. When Nabel’s group gave the 2009 virus a sugar coat, the pandemic H1N1 vaccine was not effective against the altered virus. But antibodies to previous seasonal H1N1 viruses didn’t kill the sugar-coated 2009 virus, either.

This may show the path the pandemic virus will take as it starts to evolve to evade human defenses. Already four pandemic viruses with this change have already been seen by labs in Russia and China suggesting that the virus is changing in the way seasonal flu viruses do. Nabel suggested vaccine manufacturers might need to take the first steps to prepare an updated H1N1 vaccine, making the starter virus that could be used as the production seed when a new vaccine is needed.

There is another implication of the finding of the similarity between the 1918 and 2009 pandemic viruses and the fact that antibodies against one protect against the other, experts agree. Humans who've been infected with or vaccinated against the 2009 virus are protected against an accidental return of the 1918 virus.

When CDC scientists reconstituted that virus from genetic sequences several years ago, some people voiced concerns that the work was too dangerous. A lab accident could lead to the release of the virus that killed upwards of 50 million people in 1918 and 1919, they argued. The more people who have natural or vaccine-induced protection against the 2009 pandemic virus, the less damage a 1918 virus could cause if in the unlikely event that a 1918 virus somehow escaped from the lab.

Sounds like just yet another reason to get vaccinated for H1N1!