Different kinds of flu are threatening to us every year, which means that every year we have to get shots to get immunity for it. There are no long term means to guard yourself against the virus that ever so often makes you lay in the bed when you actually cannot afford wasting time. However, now team of researchers from The Scripps Research Institute and the Janssen Pharmaceutical Companies of Johnson & Johnson (Janssen) have developed a long-lasting flu vaccine. This new way to induce antibodies to fight a wide range of influenza subtypes could one day eliminate the need for repeated seasonal flu shots.
We often regard flu as only a minor inconvenience, costing us week or two taken out of our ordinary working life. However, this virus actually causes quite a lot of problem. In United States only it causes more than 200,000 hospitalizations and 36,000 deaths every year. Of course, many people choose to get protected by yearly flu shots, but subtypes not covered by the vaccine can emerge rapidly. For example, H1N1, commonly known as “swine flu”, killed an estimated 151,700 to 575,400 people worldwide in 2009. However, there was some hope that universal vaccine is possible, because there are broadly neutralizing antibodies, or bnAbs, that only few people have.
Therefore, scientists set out to create a universal vaccine that would elicit such bnAbs. Antibodies target a site on the influenza virus that does not mutate rapidly, which, if efforts of scientists would be successful, would make for a long-lasting flu vaccine. Researchers chose a protein on the surface of influenza, called hemagglutinin (HA), as a target. This protein is common in all subtypes of influenza. Its function is to provide the key viral “machinery” that enables the virus to enter cells. What makes it really an attractive target for new vaccine, is that 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. Scientists say that if body has immunity against HA, virus has very little chances to get it infected.
In order to develop antibodies against the HA stem, scientists researched the structure of influenza, specifically the universal recognition site of the broadly protective antibody CR9114 in the HA stem. The vaccine candidate has been already designed, produced and tested. And it is a huge achievement, although it is difficult to explain to common public without the background in health scientists. This is the first time ever when scientists managed to cut off the variable head region of HA, designing features able to stabilize the conformation of the original protein, and at the same time faithfully mimicking the key broadly neutralizing site. Scientists were trying to teach body’s immune system to make powerful antibodies against influenza virus, priming it to fight off a variety of flu strains and in order to achieve that scientists had to use this synthetic version of the HA stem in a vaccine.
Scientists performed experiments to find the perfect combination of substances in the vaccine. They used rodent and nonhuman primate models and found that their vaccine made bodies of animals to produce antibodies that could bind with HAs in many influenza subtypes, even neutralizing H5N1 viruses, also known as “avian” or “bird” flu. Professor Ian Wilson said: “these tests showed that antibodies elicited against one influenza subtype could protect against a different subtype.”
Scientists used the imaging techniques of electron microscopy and x-ray crystallography to monitor the structure of the immunogen at every point in the process. They found that immunogen from their vaccinemimicked the HA stem and that antibodies could bind with the immunogen just as they would with a real virus. It is the proof that vaccine can elicit antibodies against the stem region, making it a universal vaccine against most types of the flu. Now scientists will progress onto a next step, which is to test the vaccine candidate on humans. If all tests will be successful, a lot of lives can be saved by this achievement and finally we could have one shot for protection lasting many years.