Vanderbilt scientists discover powerful new weapon

Vanderbilt University researchers have identified potent monoclonal antibodies against influenza B, presenting a promising avenue for treatment and preventative strategies to combat the virus.

Researchers at Vanderbilt University Medical Center have identified human monoclonal antibodies targeting influenza B, a major public health problem that primarily affects children, the elderly, and people with weakened immune systems.

Seasonal flu vaccines cover influenza B and the more common influenza A, but do not stimulate the widest possible range of immune responses against both viruses. Additionally, people whose immune systems have been weakened by age or illness may not respond effectively to the flu vaccine.

Small molecule drugs that block neuraminidase, a major surface glycoprotein in influenza viruscan help treat early infection, but their benefit is limited when the infection is more severe, and they are generally less effective in treating influenza B virus infections. Another way to combat this virus.

Breakthrough in monoclonal antibodies

Report in the newspaper ImmunityVUMC researchers describe how, from the bone marrow of an individual previously vaccinated against influenza, they isolated two groups of monoclonal antibodies that bound to distinct parts of the neuraminidase glycoprotein on the surface of the flu b.

One of the antibodies, FluB-400, largely inhibited virus replication in laboratory cultures of human respiratory epithelial cells. It also protects against influenza B in animal models when administered by injection or through the nostrils.

Intranasal administration of antibodies may be more effective and have fewer systemic side effects than more traditional routes – intravenous infusion or intramuscular injection – in part because intranasal antibodies can “trap” the virus in nasal mucus, preventing thus infection of the underlying epithelial surface, the researchers suggested.

These results support the development of FluB-400 for the prevention and treatment of influenza B and will help guide efforts to develop a universal influenza vaccine, they said.

“Antibodies have increasingly become an attractive medical tool for preventing or treating viral infections,” said the paper's corresponding author, James Crowe Jr., MD. “We set out to find antibodies against the influenza B virus, which continues to pose a medical problem, and we were pleased to find such potent molecules in our research.”

Crowe, the Ann Scott Carell Chair, is professor emeritus of pediatrics at the university and director of the Vanderbilt Vaccine Center, which has isolated monoclonal antibodies against a multitude of viral infections, including COVID-19.

Reference: “Isolation of human antibodies against influenza B neuraminidase and protective mechanisms at the airway interface” by Rachael M. Wolters, James A. Ferguson, Ivette A. Nuñez, Elaine E. Chen, Ty Sornberger, Luke Myers, Svearike Oeverdieck, Sai Sundar Rajan Raghavan, Chandrahaas Kona, Laura S. Handal, Trevor E. Esilu, Edgar Davidson, Benjamin J. Doranz, Taylor B. Engdahl, Nurgun Kose, Lauren E. Williamson, C. Buddy Creech, Katherine N. Gibson-Corley, Andrew B. Ward and James E. Crowe, May 31, 2024, Immunity.
DOI: 10.1016/j.immuni.2024.05.002

This study was supported in part by National Institutes of Health awards T32AI112541, K01OD036063 and U01AI150739, NIH-HHS contracts 75N93019C00074 and 75N93019C00073, and National Institute of Allergy and Infectious Diseases Collaborative Influenza Vaccine Innovation Centers Program.