Influenza A is a highly mutable virus that infects millions of people every year and can be fatal in severe cases. Human antibodies are effective against a few strains belonging to 2 of the 16 subtypes of influenza A, and new vaccines based on those antibodies are developed each year to match the evolved viruses, at considerable expense. Although various groups have isolated antibodies that are effective against multiple subtypes of influenza A, a vaccine that protects against all subtypes has long been sought. Development of such a vaccine requires the isolation of neutralizing antibodies that are broadly effective against these subtypes.

Now, a collaborative effort led by Antonio Lanzavecchia (Institute for Research in Biomedicine, Bellinzona, Switzerland) and John J. Skehel (Medical Research Council, London, UK) has identified an antibody that neutralizes all 16 subtypes of influenza A. The antibody has broad efficacy and high potency and therefore may be useful in developing a 'universal' vaccine.

Although it could be years before such a vaccine is designed and tested, the researchers believe that in the meantime, the antibody itself could be used as a treatment. By binding to the virus, the antibody prevents it from infecting mammalian cells. The antibody, called FI6, prevented mortality in mice and ferrets that were infected with flu. “The animals survived infection with multiple different flu strains at doses that would usually kill them,” Lanzavecchia said in an interview with Nature News. “In humans, even reducing the viral load by 10% could help stop people getting sick.”

Credit: Sebastian Kaulitzki

The group used a new high-throughput method to screen for rare antibodies from 104,000 cultured plasma cells from eight human donors who had been infected with or immunized against multiple strains of influenza A (Science doi:10.1126/science. 1205669; published online 28 July 2011). After isolating FI6, the scientists carried out X-ray crystallography studies to analyze how the antibody bound to the virus. They found that FI6 binds to the stem region of influenza's hemagglutinin protein, a relatively stable portion of the viral structure. In contrast, most influenza antibodies bind to the head region of hemagglutinin, which mutates frequently.

In a press release, Lanzavecchia concluded, “As the first and only antibody which targets all known subtypes of the influenza A virus, FI6 represents an important new treatment option.”