The foundation stone was laid: A Dutch-American collaboration published in Science the first proof of concept that we could replace the seasonal flu shots with a vaccine that recognizes almost every subtype.

The influenza virus is incredibly variable. A yearly refreshment of flu shots is necessary to provide a moderate protection against it, and subtypes that are not covered by the vaccine can emerge and spread rapidly. This phenomenon was evident in the 2009 flu pandemic, when the swine flu subtype killed an estimated 151,700 to 575,400 people worldwide.

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Influenza A H1N1 virus, the ‘swine flu’ © Cybercobra

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But we could soon be able to keep the highly adaptable virus under control. Scientists from The Scripps Research Institute (TSRI) in the US and the Netherlands based Janssen Pharmaceutical Companies of Johnson & Johnson jointly found a way to produce antibodies that neutralize a wide range of influenza subtypes.

The starting point of the research was the fact that some people are capable of making super-antibodies that target a site on the influenza virus that does not mutate rapidly. The researchers saw the potential of these broadly neutralizing antibodies to make a really powerful vaccine.

Therefore, they zeroed in on a possible target: a protein on the surface of influenza, called hemagglutinin (HA). HA is present on all subtypes of influenza, providing the key viral machinery that enables the virus to enter cells. The long stem region of HA, which connects the virus to cells, plays such a crucial role that mutations at the site are unlikely to be passed on.

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Ian Wilson © TSRI

“If the body can make an immune response against the HA stem, it’s difficult for the virus to escape,” explains Ian Wilson, Hansen Professor of Structural Biology and chair of the Department of Integrative Structural and Computational Biology at TSRI.

The researchers were able to cut off the variable head region of HA and design a synthetic molecule that mimics the HA stem. The ultimate goal of this imitation is to trigger an immune response that leads to the production of antibodies against a site that is present in all subtypes of the flu.

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The molecule that mimics the shape of the HA stem of the influenza virus, inducing an immune response in animal models. © TSRI

Several of these mimicking molecules were tested in mice and nonhuman primate models, and indeed, one especially stable molecule effectively produced antibodies that neutralized many influenza subtypes, as for example the wicked H5N1 viruses, a.k.a. the bird flu.

“This was the proof of principle,” said Wilson. “These tests showed that antibodies elicited against one influenza subtype could protect against a different subtype.” The next step will be to see if the results are transferable to humans and “while there is more work to be done, the ultimate goal, of course, would be to create a life-long vaccine.”

The potential antibodies could not only save us the yearly routine of vaccination. It could also protect us from future flu pandemics, like the catastrophic occurrence in 1918 that killed 50 to 100 million people.

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