Are llamas (yes, llamas) the key to a universal flu vaccine?

Researchers have developed a new nasal gene spray that immunized mice against several dozen flu strains by utilizing antibodies from an unexpected source: llamas, according to a study in Science. While the research is still in its early stages, the researchers said the breakthrough brings them one step closer to creating a universal flu vaccine for humans.

Traveling this fall? How to avoid the flu when you fly.

The need for a universal flu vaccine

The flu causes to up to 650,000 deaths each year. As of Oct. 27, this year's epidemic had claimed the lives of nearly 200 pediatric patients, according to CDC. And while the seasonal flu shot offers some protection each year, its benefits are limited. The shot's efficacy changes from year-to-year, For example, this year's seasonal vaccine reduces the risk of infection, at best, by 60%.

In addition, according to the New York Times, the vaccine's effectiveness is fleeting because there are numerous flu strains that can infect people each year, some of "which are constantly mutating and mixing genes into new combinations." It can take researchers months to create a new vaccine when a new flu strain rears its head, and, while that new vaccine is in development, the new flu strain can sicken and kill "hundreds of thousands, perhaps millions, of lives," the New York Times reports.

As a result, researchers are invested in developing a universal flu vaccine—the sort of shield that can protect people from whatever strain of the flu they might encounter.

The research

Currently, according to the New York Times, flu vaccines work by helping the recipient's immune system produce protective antibodies attach to the hemagglutinin knob on a virus's shell to obstruct its ability to enter and infect the recipient's cells. However, since different flu strains have different knobs—and since mutations can alter a strain's hemagglutinin knob from year to year—it's almost impossible for the antibodies formed against one influenza strain to defend against other strains.

To build a better flu vaccine, scientists from the Scripps Research Institute are taking a different approach. They are focusing on rare "neutralizing antibodies" found in some patients that target parts of the virus that are largely identical from one strain to the next and are less prone than the hemagglutinin knob to mutation.

And that's why the researchers turned to llamas: The researchers isolated neutralizing antibodies found in llamas because they are smaller than human antibodies, meaning the proteins are tiny enough to combine into one "mega-antibody" that could be easily inserted into small crevices of a virus, the Los Angeles Times reports. Specifically, the researchers isolated four of these antibodies—which the researchers called "nanobodies"—to create a mega-antibody.  

The researchers then engineered a gene that would be able to ferry the new mega-antibody into a host, as well as deliver the "manufacturing machinery to produce it," the Los Angeles Times reports. But then the researchers faced another problem: The human immune system—particularly as it ages—has an unreliable response to vaccines, and the researchers weren't sure how to ensure that the immune system would develop the antibody when exposed to the vaccine. To sidestep the problem, the researchers built "a gene that encoded the production plans" for the mega-antibody, the Los Angeles Times reports.  

The researchers then tucked the gene into a harmless virus, which they administered to mice via a nasal spray. After receiving the vaccine, the mice proved immune to 59 of 60 tested flu strains. In fact, the only strain against which the vaccine was ineffective was a type of bird flu that doesn't infect humans. According to Joost A. Kolkman, co-author of the study and an engineer at Jansseen, that level of flu protection "has never been seen before."

Implications

According to the Los Angeles Times, the research is significant because the mega-antibodies could protect against new and adapting flu strains. However, the vaccine's "success in mice is no guarantee of success in people," the New York Times reports. Researchers have to run clinical trials on humans to determine the effectiveness of the vaccine among humans, as well as the correct dosage for humans.

While there's no evidence yet that the vaccine would be successful in humans, Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said, the "passive transfer" of the antibodies makes the vaccine potentially effective for a broad range of individuals, including people with frail or compromised immune systems. "From a scientific and technical standpoint, this is really a very elegant study," he said—although he noted that scientists are still years away from a fully tested universal vaccine (Zimmer, New York Times, 11/01; Healy,  Los Angeles Times, 11/02; Bean, Becker's Hospital Review, 11/02).

How to avoid the flu when you fly

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