Researchers discover how some natural antibodies are able to stop flu

February 11, 2013 by Bob Yirka report
Researchers discover how some natural antibodies are able to stop flu
Structures of H2 HA–VH1-69 antibody complexes. Credit: Nature Structural & Molecular Biology, doi:10.1038/nsmb.2500

(Medical Xpress)—Researchers with the Scripps Institute have discovered that three naturally occurring antibodies are able to overcome flu mutations by attaching to a non-changing protein in the flu virus. As they describe in their paper published in the journal Nature Structural & Molecular Biology, they have found that the antibodies that are able to defeat the flu mutations can also stop an infection.

In order for a virus to infect a person, it must attach itself to cells in the respiratory tract. To do that, it uses a called hemagglutinin to attach to sugars in human cells called sialic acid. In this new research, the team found that hemagglutinin has a cavity shape, and that some naturally occurring are able to move into the cavity, preventing the virus from attaching to the cell, and thus an . More importantly, they have found that even as the flu virus mutates—to create shapes that fool antibodies sent by the body to destroy them—the cavity's size and shape remains the same. This means, that if a way could be found to exploit the same weakness found by some antibodies, a universal vaccine could be created that would work against all types of the flu viruses, instead of just one strain.

A flu virus infection is actually a little more complicated than that—the virus doesn't just attach to one part of the cell via sialic acid, it attaches to many. Multiple attachments make it almost impossible for antibodies to work against them. The researches refer to it as similar to Velcro. This is why current treatments don't work as well as hoped—their mission is to assist antibodies in removing flu viruses already attached to cells.

Making things even more difficult for the person trying to fight the infection, is that the also multiply, using mutations to thwart invading antibodies. A better approach to fighting such an infection, the researchers say, would be to create a substance similar to an antibody that could insert itself between a flu virus (in its cavity) and the cell it's trying to infect, preventing attachment. Doing so would make moot any carried out by the flu virus, as the cavity remains the same in all variations. The end result would be the prevention of an infection.

This new research shows what needs to be done to conquer the once and for all—the next step will involve trying to figure out how to create an artificial antibody, or to learn how to coax natural ones into performing as desired.

Explore further: H1N1 discovery paves way for universal flu vaccine: research

More information: A recurring motif for antibody recognition of the receptor-binding site of influenza hemagglutinin, Nature Structural & Molecular Biology (2013) doi:10.1038/nsmb.2500

Influenza virus hemagglutinin (HA) mediates receptor binding and viral entry during influenza infection. The development of receptor analogs as viral-entry blockers has not been successful, which suggests that sialic acid may not be an ideal scaffold to obtain broad, potent HA inhibitors. Here, we report crystal structures of Fab fragments from three human antibodies that neutralize the 1957 pandemic H2N2 influenza virus in complex with H2 HA. All three antibodies use an aromatic residue to plug a conserved cavity in the HA receptor-binding site. Each antibody interacts with the absolutely conserved HA1 Trp153 at the cavity base through π-π stacking with the signature Phe54 of two VH1-69–encoded antibodies or a tyrosine from HCDR3 in the other antibody. This highly conserved interaction can be used as a starting point to design inhibitors targeting this conserved hydrophobic pocket in influenza viruses.

Related Stories

H1N1 discovery paves way for universal flu vaccine: research

May 8, 2012
University of British Columbia researchers have found a potential way to develop universal flu vaccines and eliminate the need for seasonal flu vaccinations.

Pandemic 2009 H1N1 vaccination produces antibodies against multiple flu strains

May 21, 2012
The pandemic 2009 H1N1 vaccine can generate antibodies in vaccinated individuals not only against the H1N1 virus, but also against other influenza virus strains including H5N1 and H3N2. This discovery adds an important new ...

Newly discovered antibody recognizes many strains of flu virus

August 8, 2011
Some vaccines are once-in-a-lifetime; others need a booster shot or two to maintain their potency. And then there's the flu vaccine, which only lasts a year. Strains of influenza virus change so much from year-to-year that ...

Study suggests potential hurdle to universal flu vaccine development may be overcome

August 15, 2012
In the quest for a universal influenza vaccine—one that elicits broadly neutralizing antibodies that can protect against most or all strains of flu virus—scientists have faced a sobering question: Does pre-existing ...

Recommended for you

Common antiseptic ingredients de-energize cells and impair hormone response

August 22, 2017
A new in-vitro study by University of California, Davis, researchers indicates that quaternary ammonium compounds, or "quats," used as antimicrobial agents in common household products inhibit mitochondria, the powerhouses ...

Researchers offer new targets for drugs against fatty liver disease and liver cancer

August 22, 2017
There may no silver bullet for treating liver cancer or fatty liver disease, but knowing the right targets will help scientists develop the most effective treatments. Researchers in Sweden have just identified a number of ...

Make way for hemoglobin

August 18, 2017
Every cell in the body, whether skin or muscle or brain, starts out as a generic cell that acquires its unique characteristics after undergoing a process of specialization. Nowhere is this process more dramatic than it is ...

Bio-inspired materials give boost to regenerative medicine

August 18, 2017
What if one day, we could teach our bodies to self-heal like a lizard's tail, and make severe injury or disease no more threatening than a paper cut?

Are stem cells the link between bacteria and cancer?

August 17, 2017
Gastric carcinoma is one of the most common causes of cancer-related deaths, primarily because most patients present at an advanced stage of the disease. The main cause of this cancer is the bacterium Helicobacter pylori, ...

Two-step process leads to cell immortalization and cancer

August 17, 2017
A mutation that helps make cells immortal is critical to the development of a tumor, but new research at the University of California, Berkeley suggests that becoming immortal is a more complicated process than originally ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.