Scientists, from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health, reported that the ever-changing “head” of the flu virus protein has an unexpected Achilles’ heel. The team found and identified the structure of a naturally occurring human antibody that recognizes and destroys part of the hemagglutinin (HA) protein used by the virus to enter and infect cells. In addition, the researchers found that the antibody, called FluA-20, binds closely to a region of the globular head of the HA protein, which is only attacked by antibodies for a short period of time.
Image from Cell
James E. Crowe, M.D., professor at Vanderbilt University Medical Center in Nashville, Tennessee, and Ian A. Wilson from Scripps Research Institute in San Diego, California, led the team. They isolated FluA-20 antibodies from a person who had received multiple flu vaccinations. In a series of experiments, they found that FluA-20 could “enter” parts of the HA trimer molecule that could not otherwise be entered and split, preventing the virus from spreading between cells.
This finding is surprising because the trimer HA region is thought to be stable and antibodies cannot enter. In addition, this region is different from other areas of the head of HA and does not change much between different strains. So, in theory, antibody therapy for this precise region is effective for many influenza A strains. Similarly, vaccines designed to induce antibodies to this goal may provide long-term protection against any influenza strain, potentially eliminating the need for annual seasonal influenza vaccination.
In mouse studies, FluA-20 can prevent infection or disease when animals are exposed to four different subtypes of influenza A virus. The two viruses used in the experiment, H1N1 and H5N1, are the first influenza subtypes, while the other two viruses, H3N2 and H7N9, belong to the second class. Current flu vaccines must contain viral components from both subtypes in order to trigger matching antibodies. A single vaccine that produces powerful antibodies to both groups of viruses can provide a wide range of long-term protection against influenza.