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: Priming with DNA vaccine makes avian flu vaccine work better

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

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

An accessible approach to making a mini-brain

October 1, 2015

If you need a working miniature brain—say for drug testing, to test neural tissue transplants, or to experiment with how stem cells work—a new paper describes how to build one with what the Brown University authors say ...

Tension helps heart cells develop normally in the lab

October 1, 2015

The heart is never quite at rest, and it turns out that even in a lab heart cells need a little of that tension. Without something to pull against, heart cells grown from stem cells in a lab dish fail to develop normally.

Dormant viral genes may awaken to cause ALS

September 30, 2015

Scientists at the National Institutes of Health discovered that reactivation of ancient viral genes embedded in the human genome may cause the destruction of neurons in some forms of amyotrophic lateral sclerosis (ALS). The ...


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.