Despite the widespread availability of annual flu shots, influenza caused more than 500,000 hospitalizations and an estimated 38,000 deaths during the 2024-2025 flu season, according to the Centers for Disease Control and Prevention.
Influenza vaccines prime the body’s immune system to recognize and attack glycoprotein markers on the surface of the virus. Because these markers mutate rapidly, the vaccines must be adjusted every flu season.
Now, researchers at Vanderbilt Health have isolated two monoclonal antibodies that recognize three subtypes of the influenza type A virus, and which protected against death in preclinical studies.
These findings could lead to the development of cross-reactive and neutralizing antibody therapies for individuals who are severely ill from the flu, plus vaccines that are broadly protective against the constantly evolving influenza virus, the researchers reported Dec. 1 in the Journal of Clinical Investigation.
“The discovery of these antibodies identifies potential new medicines to prevent or treat influenza and also informs vaccine developers of a vulnerable site on the virus that can be targeted by new vaccines,” said James Crowe Jr., MD, director of the Vanderbilt Center for Antibody Therapeutics.
Crowe, the Ann Scott Carell Chair and University Distinguished Professor of Pediatrics and Chemistry, is co-corresponding author of the paper with Seth Zost, PhD, research instructor in Pediatrics.
The antibodies were isolated from B cells (antibody-producing white blood cells) from an individual with extensive exposure to different strains of the influenza virus and different vaccines.
From a panel of 22 monoclonal antibodies that recognized the neuraminidase (NA) glycoprotein on the surfaces of the influenza type A virus, the researchers found two that bound to three viral strains: H1N1, H3N2 and H7N9.
Through direct binding to the active site of the NA glycoprotein, the antibodies potently inhibited the activity of the viral sialidase enzyme, which facilitates its ability to infect cells and spread through the respiratory system. NA-specific monoclonal antibodies can also recruit immune cells to destroy infected cells.
“The antibodies we isolated are from B cells which were likely involved in the first immune response this individual made to any influenza virus,” Zost said. “By better understanding how antibodies like these evolve to be so broad, we can better understand human immune responses and design better vaccines and antibody therapeutics.”
“Our research team is now working with potential manufacturers to consider advancing one or more of these antibodies to the clinic for testing as new medicines,” Crowe added.
Ty Sornberger, PhD, who earned his doctorate in Microbe-Host Interactions from Vanderbilt this fall, is the paper’s first author.
Co-authors are Rachael Wolters, DVM, PhD, Iuliia Gilchuk, PhD, Luke Myers, Elad Binshtein, PhD, Ryan Irving MS, Elaine Chen, PhD, Pavlo Gilchuk, PhD; Rachel Nargi, Rachel Sutton, MS, Bethany Howard, DVM, Laura Handal, Andrew Trivette, MS, Katherine Webb, Chandrahaas Kona, Eduardo Villalobos, and Lauren Williamson, PhD.
The study was supported in part by National Institutes of Health grants T32AI112541, 7K01OD036063, and U01AI150739.
