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Researchers have found an antibody that protects mice against a wide range of lethal influenza viruses, according to a study from Washington University School of Medicine in St. Louis, Icahn School of Medicine at Mount Sinai in New York City, and Scripps Research in La Jolla, Calif. The antibody could serve as a template to aid in design of a universal vaccine that protects against all strains of the virus, and a drug to treat and protect against severe cases of flu, including pandemics.
"There are many strains of influenza virus that circulate, so every year we have to design and produce a new vaccine to match the most common strains of that year," said co-senior author Ali Ellebedy, Ph.D., an assistant professor of pathology and immunology at Washington University. "Now imagine if we could have one vaccine that protected against all influenza strains, including human, swine and highly lethal avian influenza viruses. This antibody could be the key to the design of a truly universal vaccine." Ellebedy discovered the antibody—an immune protein that recognizes and attaches to a foreign molecule—in blood taken from a patient hospitalized with flu at Barnes-Jewish Hospital in St. Louis in the winter of 2017. Ellebedy was working on a study analyzing the immune response to flu infection in humans, in collaboration with the Washington University Emergency Care and Research Core, which was sending him blood samples from consenting flu patients. He quickly noticed that this particular blood sample was unusual: In addition to containing antibodies against hemagglutinin, the major protein on the surface of the virus, it contained other antibodies that were clearly targeting something else.
"At the time we were just starting, and I was setting up my lab so we didn't have the tools to look at what else the antibodies could be targeting," said Ellebedy, who is also an assistant professor of medicine and of molecular microbiology. He sent three of the antibodies with unknown targets to co-senior author Florian Krammer, Ph.D., a microbiology professor at the Icahn School of Medicine at Mount Sinai. An expert on neuraminidase—the other protein on the surface of the influenza virus—Krammer tested the antibodies against his extensive library of neuraminidase proteins. At least one of the three antibodies blocked neuraminidase activity in all known types of neuraminidase in flu viruses, representing a variety of human and nonhuman strains. "The breadth of the antibodies really came as a surprise to us," Krammer said. "Typically, anti-neuraminidase antibodies can be broad within a subtype, like H1N1, but an antibody with potent activity across subtypes was unheard of. At first, we did not believe our results. Especially the ability of the antibodies to cross between influenza A and influenza B viruses is just mind-boggling. It is amazing what the human immune system is capable of if presented with the right antigens."....
Published on Science (Oct. 25, 2019):
