Will flu’s ‘hidden target’ lead to a universal vaccine?

(Credit: Dale Miller/Flickr)

The discovery of a “hidden target” on the surface of the hypervariable influenza A virus could lead to better ways to prevent and treat the flu, researchers say.

Because influenza A viruses such as H1N1 and H3N2 mutate continuously, vaccines sometimes provide variable or incomplete protection and need annual updates. Poor matches can lead to severe flu seasons as in 2017-2018, when an estimated 80,000 people in the United States died from flu-related complications.

A receptor binding site on the surface of the influenza virus allows it to infect cells in the body. Neutralizing antibodies target the site, which is located on the “head” of the globular hemagglutinin (HA) glycoprotein.

But because it mutates rapidly, influenza can often evade immune detection.
That’s why the discovery of a broadly protective, naturally occurring human antibody is so exciting, researchers say.

Isolated from a donor with an extensive influenza vaccination history, the antibody, called FluA-20, protected mice from four flu strains that cause disease in humans, according to a new study, which appears in Cell.

“The human body’s own natural response for flu is teaching us the way forward toward a universal flu vaccine.”

The antibody’s effectiveness results from its ability to expose and latch onto a previously “hidden” surface near the viral binding site that remains strongly conserved (with little variation) among diverse subtypes of influenza, including bird flus with pandemic potential.

“We were surprised and excited to find this new site of vulnerability on the surface of influenza, which we were able to identify by making hundreds of different antibodies from immune subjects,” says James Crowe Jr., professor in pediatrics and pathology, microbiology and immunology at Vanderbilt University and director of the Vanderbilt Vaccine Center.

Exposing and targeting this buried protein sequence could lead to broader, more effective and longer lasting vaccines and treatments, Crowe says. “The human body’s own natural response for flu is teaching us the way forward toward a universal flu vaccine.”

Additional coauthors are from Vanderbilt and Scripps Research Institute. The National Institutes of Health, the National Institute of Allergy and Infectious Diseases, the National Institute of General Medical Sciences, and the National Center for Advancing Translational Sciences funded the work.

Source: Vanderbilt University