Two years ago, fear about the the novel H1N1 flu strain spread far more quickly than the virus itself, fueled by equal parts scientific concern about its resemblance to the deadly 1918 flu and media hysteria. In those early days, with a vaccine still months away, scientists were working quickly to develop protections and treatments for the flu for those at high risk of infection and serious illness. As a Chicago Tribune reporter covering the impending pandemic, one of the flu experts I spoke to about these efforts was Patrick Wilson, assistant professor of medicine at the University of Chicago. Wilson, in collaboration with scientists from the CDC and Emory University, was looking at the antibodies produced by the first people exposed to H1N1, to see if they could be used as emergency “vaccines” for health care workers that would be exposed to infected patients.
Though the worldwide pandemic did not measure up to initial concerns, it remained a dangerous and virulent flu, infecting 60 million and hospitalizing more than 250,000 in the United States alone. And while it was not urgently needed, Wilson’s research on the antibodies for H1N1 continued, in order to learn about how the body defended itself against this viral invader. As published this week in the Journal of Experimental Medicine, that project led to a surprising conclusion: the antibodies produced to fight the 2009 H1N1 virus were not only successful in warding off that virus, but might be protective against many different types of influenza – including the historically nasty 1918 strain.
“The result is something like the Holy Grail for flu-vaccine research,” Wilson said. “It demonstrates how to make a single vaccine that could potentially provide immunity to all influenza. The surprise was that such a very different influenza strain, as opposed to the most common strains, could lead us to something so widely applicable.”
When the body reacts to an influenza virus, or any other infectious disease, it creates antibodies that target a specific segment of the invading virus or bacteria to kill or neutralize it. But because influenza viruses are constantly mutating into new forms, antibodies your immune system generated for previous seasons’ strains may not be protective against new strains. Hence, the need for a yearly flu shot, which contains inactivated forms of the viruses that scientists predict will become common in the next season. The vaccine spurs the production of antibodies against those strains, offering protection against infection.
For Wilson and his collaborators, the original idea was to take antibodies from patients exposed to H1N1 in its earliest days and use them to either protect others from infection or treat those who had already been infected. Initial experiments on the antibodies’ power of recognition proved successful – as predicted, many of the antibodies harvested from the white blood cells of H1N1 patients were able to bind the flu strain in an assay. But then, a surprise: when tested with seasonal flu strains from previous years, the antibodies could bind those viruses as well. Researchers threw the last 10 years of seasonal flu, the deadly 1918 virus, and even a dangerous but rare H5N1 avian flu at the antibodies and found they could neutralize them all.
Attacking a virus in a dish is one thing, but the big test would be whether these antibodies could fight infections in the body. Mice were given the antibodies before receiving a dose of the 2009 H1N1 strain, and were found to be protected against the virus as if given a vaccine. When mice were dosed with H1N1 first, then given antibodies as much as 3 days later, the antibodies successfully fought off the infection; by day 12, the antibody-treated mice were free of virus, while the unfortunate control mice all perished by day 7 or 8. The antibodies went on to reign victorious over influenza in further experiments with seasonal flu, the 1918 flu, and avian flu.
Why are these H1N1-triggered antibodies so much more versatile at attacking different flu strains? Binding experiments suggested that they have found a better target on the flu virus – on the “stalk,” a region that is shared between different strains rather than mutated away with each year’s new virus. By combining what the immune system learned from previous viruses with a wildly different strain like the 2009 H1N1 virus, the body may have hit upon a universal weakness that the bug cannot evade, for now.
“While the flu changes from year to year, some core elements have been consistent for nearly a century,” said Wilson.
In finding a common vulnerability for influenza strains, nature may have done what scientists could not – find the key to a universal flu vaccine. Currently, Wilson and his collaborators are dissecting the antibodies’ function to find exactly what makes them work, as well as testing antibodies from people who were given the H1N1 vaccine last season or the three-strain vaccine used this year. In the meantime, while Wilson still advised people to get their flu shots, it’s possible that those of us who either got sick with H1N1 or received a shot against it may already be benefiting from these versatile super-antibodies. In a twist ending worthy of M. Night Shyamalan, the virus that originally paralyzed with fear may actually be a hero in the fight against flu.
Wrammert J, Koutsonanos D, Li GM, Edupuganti S, Sui J, Morrissey M, McCausland M, Skountzou I, Hornig M, Lipkin WI, Mehta A, Razavi B, Del Rio C, Zheng NY, Lee JH, Huang M, Ali Z, Kaur K, Andrews S, Amara RR, Wang Y, Das SR, O’Donnell CD, Yewdell JW, Subbarao K, Marasco WA, Mulligan MJ, Compans R, Ahmed R, & Wilson PC (2011). Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection. The Journal of experimental medicine PMID: 21220454