Scientists have developed a new, faster way to create human monoclonal antibodies against infectious disease by tapping the immune system at the peak of its powers.
Researchers from Emory University School of Medicine and Oklahoma Medical Research Foundation report that they can generate high-affinity monoclonal antibodies against influenza virus a month after vaccinating human volunteers.
Their results are described in an advance online publication in the journal Nature.
"This method could find broad application towards almost any infectious disease," says Rafi Ahmed, PhD, director of the Emory Vaccine Center and a Georgia Research Alliance Eminent Scholar.
As a first example, doctors could quickly generate human antibodies against a pandemic flu strain as a stop-gap therapy or to protect people from infection. In this study, the antibodies were not tested on influenza virus strains with pandemic potential, such as the H5N1 strain although such studies are underway.
Ahmed and postdoctoral fellow Jens Wrammert, PhD, from the Emory Vaccine Center and Emory University School of Medicine, collaborated with Don Capra, PhD, and Patrick Wilson, PhD, immunology researchers at the Oklahoma Medical Research Foundation.
"With just a few tablespoons of blood, we can now rapidly generate human antibodies that can be used for immunization, diagnosis and treatment of newly emerging strains of influenza," Wilson says. "In the face of a disease outbreak, the ability to quickly produce infection-fighting human monoclonal antibodies would be invaluable."
With a detailed look at the antibodies stimulated by booster vaccination, the scientists also were able to address an issue that confounds health authorities trying to predict which viral strains will prevail in the upcoming flu season.
Doctors have worried about a phenomenon called "original antigenic sin," where immunizing someone against a certain strain can handicap them in responding to a related strain.
"We found that these early B cell responses are able to focus on the new virus, even though the immune system has seen related viruses before," says Wrammert, who is the paper's first author. B cells are the white blood cells that make antibodies.
The authors conclude that original antigenic sin is uncommon for healthy adults receiving influenza vaccination.
The methods previously used to make human monoclonal antibodies can be relatively laborious, Ahmed says. They involve sifting through human B cells and looking for those that make the right antibodies, or vaccinating mice and "humanizing" the mouse antibody genes by altering them so that they resemble human antibodies.
To make human antibodies against influenza, the Emory and University of Oklahoma researchers isolated antibody-secreting cells (plasma cells) from volunteers' blood a week after vaccination and cloned the antibody genes from these antibody-secreting cells.
"There's a transient window where the cells that are making high-quality antibody are found in the blood," Ahmed says. “They disappear from the blood afterwards, but at a certain point, most of the antibody-secreting cells are making antibody specific for flu virus."
The research was funded by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.