Knowing origin of broadly neutralizing antibodies could aid universal flu vaccine design

August 29, 2012

National Institutes of Health scientists have identified how a kind of immature immune cell responds to a part of influenza virus and have traced the path those cells take to generate antibodies that can neutralize a wide range of influenza virus strains. Study researchers from the National Institute of Allergy and Infectious Diseases (NIAID), part of NIH, were led by Gary Nabel, M.D., Ph.D., director of NIAID's Vaccine Research Center. Their findings appear online in advance of print in Nature.

"This new understanding of how an immature immune cell transforms into a mature B cell capable of producing antibodies that neutralize a wide variety of could speed progress toward a universal flu vaccine—one that would provide protection against most or all strains," said NIAID Director Anthony S. Fauci, M.D.

Universal flu vaccines, which are in development at NIAID and elsewhere, differ significantly from standard . Unlike standard vaccines, which prompt the immune system to make antibodies aimed at the variable head of a lollipop-shaped influenza protein called hemagglutinin (HA), a universal flu vaccine would elicit antibodies that target HA's stem. Because the stem varies relatively little from strain to strain and does not change substantially from year to year, a vaccine that can elicit HA stem-targeted antibodies would, in theory, provide recipients with broad protection from the flu. The neutralizing antibodies generated would recognize any strain of .

Finding ways to elicit these broadly neutralizing antibodies (bnAbs) is thus a key challenge for universal developers. However, there is a snag. Researchers knew what the end products (mature bnAbs) look like, but they did not have a clear picture of the initial steps that stimulate their development. Specifically, they lacked an understanding of how the precursor immune cell—called a naive B cell—first recognizes the HA stem and starts down a path that ends in mature bnAb-producing B cells.

In the new research, Dr. Nabel and his colleagues demonstrated that the immature antibodies can only recognize and bind to HA's stem when the antibodies are attached to the membrane of a naive B cell. The investigators showed that this initial contact delivers a signal that triggers the maturation of these naive into countless daughter cells, some of which acquire the specific genetic changes that give rise to HA-stem-binding antibodies. "We have repeated the first critical steps in the route leading to broadly neutralizing influenza antibodies," said Dr. Nabel. "Understanding how such antibodies originate could allow for rational design of vaccine candidates that would prompt the correct naive B cells to go on to mature into bnAb-producing cells."

The findings could also be relevant to HIV vaccine design, noted Dr. Nabel. There, too, eliciting bnAbs to relatively constant portions of HIV is a key goal. The insights into how naive B cells recognize constant components of a virus and mature into bnAb-producing cells could guide efforts to design an HIV vaccine capable of reproducing this effect.

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

More information: D Lingwood et al. Structural and genetic basis for development of broadly neutralizing influenza antibodies. Nature DOI 10.1038/nature11371 (2012).

Related Stories

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 ...

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.

Priming with DNA vaccine makes avian flu vaccine work better

October 3, 2011
The immune response to an H5N1 avian influenza vaccine was greatly enhanced in healthy adults if they were first primed with a DNA vaccine expressing a gene for a key H5N1 protein, researchers say. Their report describes ...

Recommended for you

Want to win at sports? Take a cue from these mighty mice

July 20, 2017
As student athletes hit training fields this summer to gain the competitive edge, a new study shows how the experiences of a tiny mouse can put them on the path to winning.

Engineered liver tissue expands after transplant

July 19, 2017
Many diseases, including cirrhosis and hepatitis, can lead to liver failure. More than 17,000 Americans suffering from these diseases are now waiting for liver transplants, but significantly fewer livers are available.

Lunatic Fringe gene plays key role in the renewable brain

July 19, 2017
The discovery that the brain can generate new cells - about 700 new neurons each day - has triggered investigations to uncover how this process is regulated. Researchers at Baylor College of Medicine and Jan and Dan Duncan ...

'Smart' robot technology could give stroke rehab a boost

July 19, 2017
Scientists say they have developed a "smart" robotic harness that might make it easier for people to learn to walk again after a stroke or spinal cord injury.

New animal models for hepatitis C could pave the way for a vaccine

July 19, 2017
They say that an ounce of prevention is worth a pound of cure. In the case of hepatitis C—a disease that affects nearly 71 million people worldwide, causing cirrhosis and liver cancer if left untreated—it might be worth ...

Omega-3 fatty acids fight inflammation via cannabinoids

July 18, 2017
Chemical compounds called cannabinoids are found in marijuana and also are produced naturally in the body from omega-3 fatty acids. A well-known cannabinoid in marijuana, tetrahydrocannabinol, is responsible for some of its ...

0 comments

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.