Scientists identified an antibody protecting mice against a range of lethal influenza viruses. This is an interesting step towards designing a universal vaccine to either treat or protect people against all strains of viruses. The study was conducted by Scripps Research with Washington University School of Medicine in St. Louis and Icahn School of Medicine at Mount Sinai in New York. It indicates a novel approach to attack severe flu cases, including pandemics.
The research is published in Science. Ian Wilson, DPhil (from Scripps Research), one of three senior co-authors, explained that the antibody studied in the research is bound to a protein called neuraminidase, which enables the flu virus to replicate.
Located on the surface of the virus, the protein enables infected host cells to release the virus so that it can spread to other cells. Tamiflu is a drug that is frequently used for severe flu infection. It inactivates neuraminidase still a number of enzyme forms still exist, depending on the flu strain. The drugs dealing with it are not universally effective, especially as there is a lot of resistance to the drugs.
"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, PhD, 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 other highly lethal avian influenza viruses. This antibody could be the key to design of a truly universal vaccine."
The antibody is an immune molecule that recognizes and attaches to a foreign molecule. It was discovered by Ellebedy in blood samples taken from a patient hospitalized with flu at Barnes-Jewish Hospital in St. Louis, in the 2017 winter.
He was involved in a study analyzing the immune response to flu in humans, even as he collaborated with the Washington University Emergency Care and Research Core that sent him blood samples from consenting flu patients. He noticed that one particular blood sample seemed strange. Apart from containing antibodies against hemagglutinin, which was an important protein on the surface of the virus, it also harboured a number of other antibodies that were on the warpath against other things.
"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, an assistant professor of medicine and of molecular microbiology.
Three of the antibodies were sent to co-senior author Florian Krammer, PhD, a microbiology professor at the Icahn School of Medicine at Mount Sinai. As he specialized in neuraminidase, Krammer took some tests of the antibodies against a wide library of neuraminidase proteins. He found that at least one of the three antibodies blocked neuraminidase activity in known types of neuraminidase in flu viruses. It represented a range of human and nonhuman strains.
"The breadth of the antibodies really came as a surprise to us," said Krammer. "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."
The team also used them in mice that were first given a lethal dose of influenza virus and then administered the antibody. They found that all three antibodies were effective against a number of strains. One antibody called "1G01" actually protected the body against 12 strains, including three groups of human flu virus, avian and other nonhuman strains.
"All the mice survived, even if they were given the antibody 72 hours after infection," Ellebedy said. "They definitely got sick and lost weight, but we still saved them. It was remarkable. It made us think that you might be able to use this antibody in an intensive care scenario when you have someone sick with flu and it's too late to use Tamiflu."
