Researchers at Vanderbilt University Medical Center have isolated human antibodies against a type of bird flu that has killed more than 200 people in China since 2012 and which may pose a worldwide pandemic threat.
The antibodies against H7subtype viruses exhibit “remarkable neutralizing potency,” and thus may represent a new way to protect people who have been exposed to or infected by avian influenza, they reported today in The Journal of Clinical Investigation.
The research was led by the paper’s senior author, James Crowe Jr., M.D., the Ann Scott Carrell Professor and director of the Vanderbilt Vaccine Center. Crowe and his colleagues have developed a method for rapidly producing large quantities of human monoclonal antibodies against specific viral targets.
Monoclonal antibodies are generated by clones of a type of white blood cell that have been fused to myeloma (cancer) cells to form fast-growing “hybridomas.” Once produced, these antibodies, like heat-seeking missiles, seek out and destroy their targets.
They’re not vaccines, which stimulate the body’s own immune defenses against a viral invader. Rather, the antibodies are potential treatments that, when injected, could provide short-term protection to people at risk of exposure. They also could be used as antiviral drugs to treat already infected patients.
Over the past couple of years, Crowe’s lab has produced human monoclonal antibodies that can neutralize, or kill, a wide range of potentially lethal viruses, including chikungunya, dengue, Ebola and its close cousin, Marburg.
In the current study, researchers in the Vanderbilt Vaccine Research Program injected 75 normal volunteers with an experimental bird flu vaccine against influenza subtype A/H7, and then collected antibody-producing white blood cells from them.
Hybridomas were created in Crowe’s lab, and the resulting monoclonal antibodies were isolated and then mixed with the viral surface envelope protein that is specific for the H7 bird flu virus. Five of the antibodies were especially potent in binding and inhibiting H7 flu.
Virus replication also was markedly reduced in mice when the most potent of the antibodies was injected before the animals were exposed to an H7 influenza virus.
Natalie Thornburg, Ph.D., a staff scientist in Crowe’s lab, was the paper’s first author. Other Vanderbilt faculty members who contributed to the study were Kathryn Edwards, M.D., and Buddy Creech, M.D., MPH.
Researchers from the Scripps Research Institute, University of California, San Diego, and the Icahn School of Medicine at Mount Sinai in New York also contributed.
The study was supported by the U.S. government grants including National Institutes of Health grant AI106002, contracts HHSN272200900047C and HHSN2720100007C and Department of Defense grant HDTRA1-10-1-0067.
