It could be the only flu shot you’ll ever need. Researchers have engineered a new cocktail of antibodies that protects against multiple strains of the influenza virus, including the much-feared bird flu and the 1918 Spanish flu that killed millions worldwide. It may even hold the clue to sparing you the annual vaccination.
Influenza, commonly called “the flu,” is a virus that infects the respiratory tract. Worldwide, the flu is responsible for up to 500,000 deaths annually and hospitalizes millions more, according to the World Health Organization. Each year, the virus mutates into new forms resistant to flu vaccines and natural antibodies, making it extremely difficult to treat. This is why vaccines must be re-engineered and re-administered for each yearly flu season, and even this strategy shows limited effectiveness. But soon, a single shot could make you immune to the virus for the rest of your life.
A team led by researchers at Dana-Farber Cancer Institute developed the new antibody treatment by drawing on a library of 27 billion human antibodies. They injected one of several antibodies being studied into mice that had been infected with the H5N1 strain – the deadly bird flu – three days earlier. Not only did the mice recover, but the antibody protected the mice from more than just that single strain. “What surprised us is that the same antibody protected mice from a lethal infection with a very different virus such as the H1N1 subtype that causes seasonal human infections; this is really remarkable,” said Ruben Donis, chief of the Molecular Virology and Vaccines Branch at the Center for Disease Control.
Most flu vaccines are specific to a particular strain, and must be re-engineered every year in response to new mutations in the virus. This new antibody treatment from the Dana Farber Cancer Institute is unique because it attacks a non-mutating section of the virus, preventing it from deploying the genetic material that infects the body’s cells and spreads the virus. This provides the immune system with the weapons to target multiple strains of influenza, and to protect against newly mutated strains – including strains that haven’t even evolved yet. Researchers say human testing of the drug could begin in time for the 2011-2012 flu season.
After an individual breathes in influenza, a protein called hemagglutinin on the surface of the virus help it to bind to target cells along the respiratory tract. Once the protein binds to the cell, the membranes of the virus and the cell fuse together. This creates a bridge that allows viral RNA to enter the cell and find the nucleus, where the cell’s genetic code is stored. In the cell’s nucleus, the viral RNA is copied along with the cell’s own genome. This allows a virus to spread quickly, using the body’s own cellular mechanisms to make more copies of itself.
Hemagglutinin is composed of a head region and a stem region. The head of the protein is capable of mutation; this allows the virus to evolve into new forms that the body cannot recognize through established antibodies. In contrast, the stem of the protein doesn’t mutate; it undergoes structural changes to help deliver the viral RNA, and any mutations would interfere with that function. The researchers’ new antibodies bind to the stem region of the hemagglutinin, interfering with the delivery system in a way that the virus cannot evolve around.
Flu pandemics arise when a new strain of virus evolves that our species have very little tolerance for. The Spanish flu of 1918 – the H1N1 subtype – killed between 50 and 100 million people worldwide. The avian influenza strain, or H5N1 subtype, has killed millions of birds throughout the world and aroused fears that it might mutate into a form easily transmittable to humans. Neutralizing influenza without allowing it the ability to mutate would be our species’ first line of defense against possible flu pandemics of the future.
Before a single flu shot can offer protection for a lifetime, more antibodies must be produced to neutralize strains that haven’t been tested yet. While the present research offers treatment for the H1 and H5 strains, there are sixteen types of hemagglutinin known (H1 through H16). Already, researchers are applying their new technique to the remaining strains. As they are, the antibodies that have been developed can act as a treatment for people already infected with the flu – pending FDA testing, of course.
It is unclear how effective the technique will be in treating other viruses, as there are multiple ways for a virus to infect a cell. Still, the new technique – finding a nonmutating component of a virus and causing it to malfunction – seems promising as a theoretical approach to how we fight viral infection on a global scale.
The study was published in the journal Nature Structural and Molecular Biology. The video below, released by the Dana Farber Cancer Institute, explains the how the antibody works on a molecular level.
