Vanderbilt Scientists Discover Powerful New Weapon

FluB 393 Antibody

Vanderbilt researchers have identified potent monoclonal antibodies against influenza B, particularly FluB-400, offering a new method to prevent and treat the virus. This advancement may also aid in creating a universal flu vaccine. A 3D rendering shows one of the isolated antibodies, FluB-393, (blue) binding to the neuraminidase surface glycoprotein (red) of the influenza type B virus to prevent infection. Credit: Illustration by Elad Binshtein, PhD, and Anthony Czelusniak

Vanderbilt University researchers have identified potent monoclonal antibodies against influenza B, showcasing a promising avenue for treatment and preventative strategies in combating the virus.

Researchers at Vanderbilt University Medical Center have identified human monoclonal antibodies that target influenza B, a major public health concern that primarily impacts children, the elderly, and those with weakened immune systems.

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

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

Breakthrough in Monoclonal Antibodies

Reporting in the journal Immunity, the VUMC 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 influenza B.

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

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

These findings 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 increasingly have become an interesting medical tool to prevent or treat viral infections,” said the paper’s corresponding author, James Crowe Jr., MD. “We set out to find antibodies for the type B influenza virus, which continues to be a medical problem, and we were happy to find such especially powerful molecules in our search.”

Crowe, who holds the Ann Scott Carell Chair, is University Distinguished Professor of Pediatrics and director of the Vanderbilt Vaccine Center, which has isolated monoclonal antibodies against a host of viral infections, including COVID-19.

Reference: “Isolation of human antibodies against influenza B neuraminidase and mechanisms of protection 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, 31 May 2024, Immunity.
DOI: 10.1016/j.immuni.2024.05.002

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

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