A universal flu vaccine would provide protection against all strains of flu, but an antibody that is broadly effective has so far escaped researchers. However, new research has revealed an antibody that could be effective against all strains of flu, including human, swine, and avian forms.
Every year, individuals at a high risk of suffering complications from influenza needs to have a flu vaccination. The vaccine provides protection by allowing the immune system to recognize and attack specific antigens on the surface of the flu virus.
However, a new vaccine is required each year due to the high rate of mutation. If a flu virus is encountered that the antibodies do not recognize, it will not provide any protection. The flu vaccines administered each year provide protection against the strains of flu that are circulating.
Researchers have now identified an antibody that could be used in a universal flu vaccine. The antibody has been shown to offer protection against all known flue strains in mice.
The antibody – named IG01 – binds to neuraminidase, which is needed by the flu virus to replicate and infect cells inside the host. Neuraminidase is an enzyme that allows the virus to bind to the cell membrane, ensuring it is released from the cell and can spread to other cells. The leading anti-flu drug Tamiflu also targets neuraminidase. In contrast to Tamiflu, which is not always effective as there are many different types of neuraminidase, the antibody provides much broader protection against a wide range of different flu strains, subtypes, and types.
The antibody was discovered in the blood of a patient at Barnes-Jewish Hospital in St. Louis in 2017 by Ali Ellebedy, PhD, an assistant professor of pathology and immunology at Washington University. Antibodies were present in the blood for hemagglutinin but also for neuraminidase. The antibody was sent to neuraminidase expert, Florian Krammer, PhD at the Icahn School of Medicine at Mount Sinai who determined that it blocked neuraminidase activity in all known types of flu viruses.
The antibody was tested in mice who had been given a lethal dose of the virus and all mice survived, even if the antibody was provided 72 hours after the flu dose was administered. The mice still got sick, but they did not die. That would make it more effective than Tamiflu, which needs to be provided within 24 hours to be effective.
An analysis of the antibody at Scripps Research revealed the structure contained a loop that blocked the active site of neuraminidase, thus preventing it from triggering the release of the virus from cells. The part of neuraminidase that is blocked is consistent across virtually all flu viruses, as major changes would prevent neuraminidase from achieving its purpose.
“We were surprised at how these antibodies managed to insert a single loop into the conserved active site without contacting the surrounding hypervariable regions, thereby achieving much greater breadth against the neuraminidase of different influenza viruses than we have seen before,” said Ian Wilson, DPhil, Scripps Research, and senior co-author of the study.
The researchers are now working on IG01 to develop a new flu vaccine that could provide near universal protection.
The study is detailed in the paper – Broadly protective human antibodies that target the active site of influenza virus neuraminidase – which was recently published in the journal Science. DOI: 10.1126/science.aay0678