TORONTO - The pandemic H1N1 virus more closely resembles the 1918 Spanish flu virus than more modern cousins in the same flu family, new research shows -- a finding which helps explain the age pattern of H1N1 infections.
Like the Spanish flu virus, the pandemic H1N1 lacks two sugar coats seen on contemporary viruses from the same family, the work reveals.
The two studies, released Wednesday, confirm that antibodies which protect against the pandemic virus also fight the virus that caused the 1918 pandemic. But they are not able to neutralize seasonal H1N1 viruses, nor are 2009 H1N1 viruses stopped by antibodies generated in response to those recent 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, admitted Dr. Gary Nabel, senior author of one of the papers.
"It's very rare for viruses that are separated by more than a couple of years to cross-neutralize," said Nabel, a scientist with the U.S. National Institute of Allergy and Infectious Diseases (NIAID).
The findings help 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.
The work, published in the journals Science Translational Medicine and Science, was done by researchers from NIAID and the U.S. Centers for Disease Control on the one hand and from Scripps Research Institute in La Jolla, Calif., on the other.
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 defences against flu viruses, forcing the viruses to alter themselves in order to evade those defences. 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 pigs, said Adolfo Garcia-Sastre, a flu expert at Mt. Sinai Hospital in New York City who published a study in January showing that a vaccine against the 1918 virus protected against the 2009 H1N1.
Nabel's lab was coming to the same conclusion around the same time and decided to try to figure out why. So he and his group -- and the Scripps group led by Ian Wilson -- looked at the structure of the key protein on the outside of flu viruses, the hemagglutinin. While looking at the head of that protein, they found striking similarities between the 1918 virus and the 2009 H1N1.
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 (generally the H in a flu virus's name).
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.
"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 defences, Nabel said, noting that as his group was submitting their paper for publication, they discovered four pandemic viruses with this change have already been seen by labs in Russia and China.
He suggested that may be evidence the virus is changing in the way seasonal flu viruses do.
"Well, it's certainly a warning sign, yes. We were actually amazed when we saw that," he said.
"When you make a prediction like that and within the course of a month or two you see those mutations occurring, you need to take those seriously."
Nabel suggested vaccine manufacturers may 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.
Further, he said, the finding suggests how pandemic viruses might evolve into seasonal ones, providing a road map for vaccine makers so they could try to get ahead of the virus.
But Garcia-Sastre wasn't sure, noting that sugar coating isn't the only trick flu viruses have up their sleeves. There are other changes viruses undergo as they evolve: Science can't currently foretell which will happen and in which order, he said.
"Which direction the virus is going to go, I think everybody would like to know. Nobody has been able yet to predict it," he said. "There are many different possibilities."
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, suggested Dr. John Treanor, a flu vaccine expert at the University of Rochester in New York State.
"In the extremely unlikely event that a 1918 virus somehow escaped from the lab, this experience would probably provide some measure of protection against that," he said.
